Energy expenditure, body composition, and healthy weight

Basal metabolic rate

(BMR) represents the amount of energy needed to sustain basic life processes such as respiration, heartbeat, renal function, brain and nerve function, blood circulation, active transport, and synthesis of proteins and other complex molecules. Basal metabolism accounts for the majority of energy expenditure in the human body (Figure 8.3). Most of the energy used at rest is attributed to the liver (27%), brain (19%), kidneys (10%), heart (7%), and skeletal muscle (18%), which even at rest require appreciable amounts of energy for protein synthesis and normal cellular function. Several factors can affect basal metabolism, including body composition and surface area, age and gender, pregnancy and lactation, environmental temperature, and dietary energy restriction. Many of these factors can be attributed to the amount and proportion of lean body mass, which has higher metabolic activity than adipose tissue. People with greater body weight because of increased lean body mass have a higher BMR. In aging, fat mass increases at the expense of fat-free mass, causing BMR to decrease. Women generally have a higher proportion of body fat relative to fat-free mass and, consequently, have a lower BMR than men of the same age, height, and total body weight. Tall, thin people have more surface area relative to volume, which is associated with greater heat loss and higher BMR. Cold environments can increase BMR due to shivering, which generates internal body heat. Paradoxically, hot environments can also increase BMR, possibly due to increased blood circulation and sweat gland activity. BMR increases during pregnancy and when lactating. BMR decreases during starvation due to the loss of lean body mass. BMR also decreases with aging due to reductions in some bodys' organ functions and mass. BMR is assessed indirectly by measuring oxygen consumption under carefully controlled conditions that eliminate any contribution of energy expenditure due to physical activity, thermic effect of food, or heat production that occurs in cold environments. BMR is measured when awake and in a post-absorptive state between 12 and 18 hours following food intake, preferably in the morning shortly after waking from sleep. A person must be completely relaxed in a supine position for at least 30 minutes in a thermoneutral environment. Any factors that could influence the person's internal work are minimized as much as possible. Oxygen consumption (recorded as mL per minute) is then measured for at least 10 minutes. The next step is to convert the rate of oxygen consumption into energy expenditure, based on the principle that the oxidation of carbohydrate, fat, and protein yields approximately 5 kcal of energy per liter of oxygen consumed. BMR is often expressed as daily energy expenditure (kcal/day) and, accordingly, is called basal energy expenditure. Measuring BMR accurately requires strictly controlled laboratory conditions, making it difficult to obtain in most people. As an alternative, resting metabolic rate (RMR) is more easily measured and can provide information that is nearly the same as BMR, albeit slightly higher than BMR. To measure RMR, an individual needs to fast only 3-4 hours, much less than the more stringent fasting time required for BMR. Resting comfortably just prior to recording oxygen consumption is required, but it is not necessary to conduct the measurements just after waking in the morning. RMR is usually about 10% higher than BMR because of its less stringent conditions of measurement. The term resting energy expenditure is used when RMR is converted to daily energy expenditure (kcal/day).

criteria for diagnosis of metabolic syndrome

*elevated waist circumference: ≥102 cm (40 in) for men and ≥88cm (35 in) for women *elevated TAGs ≥150 mg/dL *reduced HDL-C <40 mg/dL in men and <50 mg/dL in women *elevated blood pressure systolic ≥130 and/or diastolic ≥85 mm Hg *elevated fasting glucose ≥100 mg/dL

bulimia nervosa

Bulimia nervosa, another eating disorder, is a condition characterized by recurring binge eating coupled with self-induced vomiting and misuse of laxatives, diuretics, or other medications to prevent weight gain. Binge eating is marked by a sense of lack of control over eating during the binge episode. A binge is defined as eating an amount of food larger than most people would eat during a similar time period and under similar circumstances. Bulimia denotes a ravenous appetite (or "ox hunger") associated with powerlessness to control eating. Bulimia occurs primarily in young women, especially college-age women who are of normal weight or slightly overweight. The typical bulimic, rather than being overly concerned with losing weight and becoming very thin (like the person with anorexia nervosa), seeks to be able to eat without gaining weight. Other factors associated with the development of bulimia include a history of sexual abuse, psychoactive substance abuse or dependence, a family history of depression or alcoholism, obsessive-compulsive disorder, negative self-evaluation, and a high use of escape-avoidance coping. Bulimia often starts with dieting attempts in which hunger feelings get out of control. These dieting attempts, usually based on food abstinence or excessive food restriction, lead to binge eating. Once binge eaters discover that they can undo the consequences of their overeating by vomiting the ingested food, they begin to binge not only when they are hungry but also when they are experiencing any distressing emotion. Most binge eating is done privately in the afternoon or evening, with an intake of about 3,500 kcal; purging behaviors reduce retention of energy to about 1,200 kcal. Favorite foods for binging usually are dessert and snack foods very high in carbohydrates. Diagnosis is usually dependent upon self-reported symptoms or on treatment for related problems or conditions. Conditions that may develop as the result of bulimia are listed in Table 4. The gastrointestinal tract is greatly affected by repeated vomiting and the use of laxatives. Repeated vomiting also causes other problems, including skin lesions or calluses on the dorsal side of the hands (especially over the joints), severe dental erosion, swollen enlarged neck glands (due to salivary or parotid gland enlargement), reddened eyes, headache, and fluid and electrolyte imbalances. Laxative misuse may exacerbate fluid and electrolyte losses and, when coupled with vomiting, may lead to heart arrhythmias and heart failure. The presence of lesions or calluses on the hands (due to the scraping of teeth against the skin while self-inducing vomiting), swollen neck glands, and frequent trips to the bathroom after meals often are recognized by health professionals and family or friends and facilitate detection and diagnosis of the problem. The treatment of bulimia, like that of anorexia nervosa, is multidisciplinary. Goals typically focus on eliminating binge-purge behaviors, normalizing eating habits, maintaining weight, and resuming normal menses, if they are affected. The patient is most likely to be hospitalized with problems such as electrolyte imbalance, drug (e.g., laxatives, diuretics) dependence, severe depression, or suicidal tendencies. The prognosis of those suffering from bulimia nervosa is generally more favorable than for those with anorexia nervosa; over 50% of those with bulimia nervosa fully recover or achieve good outcomes, while fewer than 10% have poor outcomes.

body mass index

first described in the 1860s and known as Quetelet's Index, is one of the most widely accepted approaches to categorizing weight for a given height. The body mass index is considered an indication of body adiposity but does not directly measure body fat. BMI is calculated from a person's height and weight as shown in this formula: BMI = weight/height^2 with weight measured in kilograms (kg) and height measured in meters (m) and raised to a power of 2. BMI is expressed in units of kg/m2. Adult male 165 lb (74.9 kg) 5 ft ,11 inches tall (1.803 m) will have a BMI = 74.9/1.803^2= 23.0 kg/m^2. 1 lb = 0.454 kg 1 inch = 0.0254 m Body mass index is considered a good index of total body fat in both men and women and has generally replaced the practice of classifying people as underweight or overweight compared to a reference weight. The National Institutes of Health classification of body weight based on BMI for adults is presented in Figure 8.4. BMI is also used to assess weight in children, but through comparison to population standards for sex and age. BMI changes with age in healthy children, as demonstrated by the growth charts for boys and girls 2-20 years of age shown in Figure 8.5. BMI < 5th percentile is underweight; BMI between the 5th and 85th percentiles is considered healthy weight; BMI between the 85th and 95th percentiles are classified as overweight, and BMI > 95th percentile is considered obese. Bodyweight and recumbent length for boys and girls under 2 years of age are assessed using growth charts similar to those in Figure 8.5. Although the body mass index is a valuable tool for categorizing body weight, it does not directly determine body fatness. People who have large amounts of lean body mass and a low percentage of body fat may fall into the overweight category. Consequently, intermediate BMI values in the normal and overweight categories are not as strongly correlated with actual body fat percentage as compared to BMI of ≥30 kg/m2. The relationship between BMI and body fat has also been shown to vary among different ages, sex, and racial/ethnic groups. Nevertheless, measurements of BMI sampled from the U.S. population clearly indicate an alarming trend of increasing obesity prevalence in all age groups (Figure 8.6). Note in the figure that BMI ≥25 kg/m2 includes both the overweight and obese categories and that the obese category (BMI ≥30 kg/m)2 is shown separately. Because of the limitations of using BMI alone, many health professionals measure waist circumference in addition to BMI. By utilizing both of these measurements, disease risk relative to normal weight and waist circumference can be determined, as indicated in Table 8.5. Monitoring changes in waist circumference over time is helpful since it can be an indicator of abdominal fat even in the absence of a change in BMI. Including waist circumference measurements is particularly useful in people who are categorized as normal or overweight on the BMI scale because it helps distinguish those who have increased muscle mass versus excess body fat. For individuals with a BMI of ≥35 kg/m2, waist circumference adds no further predictive power of disease risk beyond BMI alone; therefore, it is unnecessary to measure waist circumference in people with a BMI of ≥ 35 kg/m2.

measuring energy expenditure

important tools for health professionals in developing dietary and exercise strategies for maintaining healthy weight and improving athlete performance. -direct calorimetry -indirect calorimetry -doubly labeled water "gold standard" for determining total energy expenditure

Cholecystokinin

stimulate digestive processes when food is consumed. CCK is produced in the small intestine in response to food intake, especially lipids and proteins. Another important function is appetite regulation. CCK binds to receptors in the hypothalamus and inhibits NPY production by down-regulating mRNA expression. CCK also binds to receptors in the pylorus, causing contractions that send vagal nerve signals from the stomach to the brain, resulting in decreased hunger and increased satiety.

thermic effect of food

A third component of energy expenditure is the thermic effect of food. This represents the metabolic response to food and is also called diet-induced thermogenesis, specific dynamic action, or the specific effect of food. The thermic effect of food represents the increase in energy expenditure associated with the body's processing of food, including the work associated with the digestion, absorption, transport, metabolism, and storage of energy from ingested food. The percentage increase in energy expenditure above BMR caused by the thermic effect of food is typically about 10% Protein in foods has the greatest thermic effect, increasing energy expenditure 20-30%. Carbohydrates have an intermediate effect, raising energy expenditure 5-10%, and fat increases energy expenditure 0-5%. The value most commonly used for the thermic effect of food is 10% of the caloric value of a mixed diet averaged over a 24-hour period [8]. Because of its relatively small contribution, the thermic effect of food is usually not included in calculations of total energy expenditure.

RQ and substrate oxidation

An RQ = 1.0 suggests that CHO is being oxidized because the amount of O2 required for the combustion of glucose = the amount of CO2 produced: C6H12O6 + 6 O2 ---> 6CO2 + 6 H20 RQ+ 6CO2/6O2= 1.0 The RQ for fat is <1.0 because FAs, compared to CHO, require more oxidation relative to the number of C atoms when producing CO2 and water. For example, TAG such as tristearin, requires 163 mol of O2 and produced 114 mol of CO2 per two tristearin molecules: 2 C57H110O6 + 163 O2 ---> 114 CO2 + 110 H20 RQ= 114 CO2/163 O2= 0.70 Calculating the RQ for protein oxidation is more complicated because metabolic oxidation of AAs requires removing the N and some O and C as urea, a compound excreted in the urine. Urea N represents net loss of energy to the body, and only the remaining CO2 structure of the AA can be oxidized in the body. Ex: C17H112N18O22S + 77 O2 ---> 63 CO2 + 38 H2O + SO3 + 9 CO(NH2)2 RQ= 63 CO2/ 77 O2 = 0.818 The RQ for an individual consuming an ordinary mixed diet consisting of all three macronutrients will range between 0.70 and 1.0. An RQ of 0.82, represents the metabolism of a mixture of 40% carbohydrate and 60% fat. RQ values that approach 1.0 indicate a higher contribution of carbohydrates for fuel, whereas an RQ closer to 0.70 indicates more fat being used for fuel. In clinical practice, an RQ < 0.8 suggests that a patient may be underfed. An RQ < 0.7 suggests starvation; consumption of low-carbohydrate, high-fat, calorie-restricted diets; or alcoholism, due to ethanol having an RQ of 0.67 Occasionally the RQ value can be greater than 1. For instance, when you hyperventilate you exhale more CO2 without using more O2, resulting in an RQ greater than 1. This may also occur when the body is in acidosis, such as following exhaustive exercise when lactic acid builds up. NaHCO2 neutralizes the lactic acid to form sodium lactate and carbonic acid (H2 3 CO). The carbonic acid is converted to CO2 and H O2 and exhaled, which results in a loss of CO2 that is not related to oxygen uptake.

thermoregulation

An additional component of energy expenditure that is of some importance is thermoregulation, also called adaptive, nonshivering, facultative, or regulatory thermogenesis. Thermoregulation refers to the adjustments in metabolism necessary to maintain the body's core temperature of about 98.2-98.68F. A drop of temperature of 108F or an increase of just 58F can be tolerated, but fluctuations beyond this range can result in death. Most people adjust their clothing and environment to maintain comfort and thermoneutrality, although the body can adjust metabolic heat production when needed by hormonal changes controlled by the hypothalamus. Measurements of BMR or RMR are performed in a thermoneutral setting so that the contribution of thermoregulation can be excluded from calculations of energy expenditure. As a cautionary note, muscular activity can generate significant heat and cause a rapid increase in body core temperature beyond the ability of the body to thermoregulate, especially in hot environments. Heat stress is a concern among high school athletes, particularly football players who have the highest incidence of heat-related deaths [9]. Coaches, parents, and athletes should take the necessary steps to ensure proper hydration and to avoid conditions that increase the risk of heat stress.

laboratory methods; densitometry: air displacement

Another way to determine the volume—and thus density—of the body is with air displacement plethysmography. In the commercially available apparatus shown in Figure 8.10 (BOD POD, Cosmed Inc.), the subject is seated in a sealed chamber of known volume, separated from a second chamber by a membrane. The instrument measures the change in pressure caused by the volume occupied by the person. The person is dressed in a tight-fitting bathing suit and wears a bathing cap (to displace pockets of air in the hair). The measurement takes only a few minutes to complete. The apparatus has an advantage in that it can measure the body composition in age groups that are not suitable for underwater weighing, such as older adults or the very young. A similar instrument called the PEA POD is designed for infants and small children. Once the density of the body is obtained, the calculation of percent body fat is the same as with underwater weighing using established equations.

harris-benedict equations

Based on indirect calorimetry, the equations were developed by Harris and Benedict in 1919 using mostly normal-weight white men and women. The Harris-Benedict equations have undergone extensive validation and found to yield reasonably accurate results in nonobese individuals, but the equations overestimate RMR in obese individuals. Separate equations are used for men and women: Men: RMR, kcal/day = 66.5 + (13.7 x W) + (5.0 x H) - (6.8 x A) Women: RMR, kcal/day = 665 + (9.56 x W) + (1.8 x H) - (4.7 x A)

anorexia nervosa

Being too thin is dangerous, even deadly. Anorexia nervosa is a chronic, relapsing illness for many individuals. Of the many psychiatric disorders, anorexia nervosa possesses the highest mortality rate. If left untreated, up to one-fifth of people with the condition die, often before 30 years of age, and many, despite treatment, die from eating disorder-related complications or suicide. Anorexia nervosa, described over 100 years ago as a loss of appetite caused by a morbid mental state, is actually misnamed because its victims do not typically experience a loss of appetite. People with anorexia nervosa have a distorted body image and an irrational fear of weight gain. This distorted body image is a perception that they are fat even though they are extremely thin. Furthermore, anorectics are extremely critical of their body as a whole and often more critical about selected body areas (such as thighs, stomach, etc.). Thus, they become obsessed with weight loss and relentlessly pursue thinness, often eating diets providing less than 800 kcal per day. Eating patterns of people with anorexia nervosa mostly fall into one of two categories: the restricting type or the binge eating-purging type. Anorectics with the restricting type eat to a very limited extent without regularly inducing vomiting or misusing laxatives or diuretics. People with the binge eating-purging type alternate between restricting food intake and bouts of binge eating or purging behavior with laxative or diuretic misuse or self-induced vomiting [4]. However, in addition to these controlled eating behaviors, anorectics often exercise excessively to further weight loss efforts, to prevent possible weight gain, and to try to correct perceived imperfections in body size and shape. Exercise is considered excessive if its postponement is accompanied by intense guilt or when it is undertaken solely to influence weight or shape. Some of the diagnostic criteria for anorexia nervosa (Table 1) based on DSM-5 include refusal to maintain body weight at or above minimally normal weight for age and height (e.g., at least 85% of expected weight for height; or, from the International Classification of Diseases, a body mass index of at least 17.5 kg/m2), intense fear of gaining weight or being fat, and amenorrhea (absence of at least three consecutive menstrual cycles). Self-worth based on weight or shape, preoccupation with food, and abnormal food consumption patterns are also typical of those with anorexia nervosa The causes of anorexia nervosa are unknown, but the disease is thought to be multifactorial. Genetic vulnerability as well as anxiety, obsessive-compulsive personality disorders, and perfectionism traits are typically present in those who develop anorexia nervosa. Anorectics also may exhibit depression and substance abuse. In addition, those who develop anorexia nervosa often have a poor self-image and want to please others because their perceived self-worth is heavily dependent upon the words and actions of others (such as teachers, coaches, or instructors). Other traits associated with the development of this eating disorder include issues concerning food and body weight, issues concerning relationships with oneself and with others, conflict regarding maturation, and problems with separation, sexuality, self-esteem, and compulsivity. The initial weight loss of the anorectic may not always result from a deliberate decision to diet; initial weight loss may occur unintentionally, for example, as the result of the flu or a gastrointestinal disorder. However, following the initial weight loss, whatever its cause, additional diet restriction (and excessive exercise) is deliberate. Weight loss or control of body weight becomes the overriding goal in life, especially during stressful periods when pressures become overwhelming. The anorectic learns the caloric contents of foods and the energy expenditure associated with various activities. Because anorectics have such a disturbed body image and such an intense fear of becoming fat, they may continue starving themselves to emaciation and even death should intervention be delayed too long. The effects of anorexia nervosa on the body are similar to the effects of hypometabolic states (such as starvation, protein-calorie malnutrition, or marasmus) and affect all parts of the body. Table 2 lists some potential consequences of anorexia nervosa. Growth and development slow. Adipose tissue, lean body mass, and bone mass are lost. Organ mass may be lost, and organ function may become impaired. Loss of heart muscle can weaken the heart and cause, among other serious complications, an irregular heartbeat or a prolonged QT interval (the QT interval is the time that it takes for the heart to contract and refill with blood; with a prolonged QT interval, the heart takes longer to recharge between beats in preparation for the next heartbeat). The gastrointestinal tract atrophies such that peristalsis is slowed, gastric emptying is delayed, and intestinal transit time is lengthened. The secretion of digestive enzymes and of digestive juices also is diminished. Constipation often results, along with abdominal distention after eating just small amounts of food. Hormone and nutrient levels in the blood become altered. Skin typically becomes dry, hair loss from the head occurs while lanugo type (soft woolly) hair may appear on the sides of the face and arms, and body temperature drops. A long-term consequence of the bone loss that occurs with anorexia nervosa is osteopenia and ultimately osteoporosis, which occurs much earlier in those who have (or have had) anorexia nervosa than in those who have not had the condition Treatment of anorexia nervosa is multidisciplinary (involving a physician, dietitian, nurse, psychologist, psychiatrist, and family therapist, among others) and may be accomplished through outpatient or inpatient care, depending on the severity of the condition. Assessment for inpatient treatment generally includes an evaluation of the person's mental status, how much the person is eating, current weight (inpatient treatment is warranted if weight is <25-30% of ideal), speed of weight loss, motivation, and adherence to treatment, family support, purging behavior, and comorbid complications, especially those affecting the heart. Whether the patient is treated as an inpatient or as an outpatient, goals for the patient's health are established, often with a written contract signed by the patient as well as by members of the health care team. Summaries of treatment outcomes for anorexia nervosa show that about 40-50% recover completely, about 30% improve, 20-25% continue to experience chronic problems with the condition, and another 10-15% die from medical complications, suicide, or malnutrition. Mortality typically is highest among people who have sustained severe weight loss, who have had the condition for a prolonged duration, and who developed the condition at an older age

bioelectrical impedance; field methods

Bioelectrical impedance analysis is another commonly used field technique that assesses the two-compartment model. The method is based on the principle that the flow of electricity (conductivity) is facilitated in fat-free tissue high in water and electrolyte content, but is impeded by fat tissue low in water and electrolytes. Electrical conductivity is measured by various techniques. For example, an instrument generates a painless current or multiple electrical current frequencies that are passed through the body by means of the electrodes. Other devices are available in which the subject stands barefoot on a scale or grasps a hand-held device that measures electrical conductivity (Figure 8.8). In each case, opposition to the electric current, called impedance, is detected and measured by the instrument. Impedance is the inverse of conductance. The lowest resistance value of a person is used to calculate conductance and predict lean body mass or fat-free mass. For example, muscles, organs, and blood, which have high water and electrolyte contents, are good conductors. Tissues containing little water and electrolytes (such as adipose tissue) are poor conductors and have a high resistance to the passage of electrical current. When multiple frequencies are used, the higher frequencies can estimate both intracellular and extracellular water because the higher-frequency current can penetrate cell membranes. At lower frequencies, the flow of the current is blocked, and the measured resistance indicates extracellular water.

other imaging techniques

Computed tomography, AKA CT or CAT scan, and magnetic resonance imaging (MRI) have been used to measure body composition. Both of these imaging techniques are used extensively in medical diagnostics, but the equipment is very expensive and requires highly trained technicians to operate. Consequently, both imaging methods are used primarily for research purposes. Knowledge about body composition led to the concept of the reference man and woman as a standard benchmark for educational and research purposes [20]. These reference figures are based on average physical dimensions from thousands of volunteer subjects and provide a frame of reference for comparison. They should not be viewed as "ideal" body composition. The characteristics of the reference man and woman were discussed in Chapter 6 and are summarized in Table 6.8. The reference man has 3% essential fat, 12% storage fat (for a total of 15% body fat), 44.8% muscle, 14.9% bone, and 25.3% other components. The reference woman has 12% essential fat, 15% storage fat (for a total of 27% body fat), 36% muscle, 12% bone, and 25% other components. Essential fat includes the fat that is associated with bone marrow, the central nervous system, internal organs, and the cell membranes. The essential fat in females also includes the fat in mammary glands and the pelvic region. These gender differences must be considered when body composition is evaluated.

components of energy expenditure

Daily total energy expenditure is attributable to three primary components: basal metabolic rate, physical activity, and the thermic effect of food. A fourth component, thermoregulation, is sometimes included.

ideal body weight formulas

Despite falling out of favor, the use of ideal body weight (IBW) formulas may still have a role in certain situations. As previously mentioned, IBW formulas evolved directly from height-weight tables and are intended to provide guidance to health practitioners when determining overall mortality risk in a given population. IBW is more easily understood by the general public than body mass index and may be the method of choice by some health professionals. Table 8.4 describes several common formulas that have been used for calculating IBW [13,14]. Note that the Broca formula provides a range for IBW at a given height, whereas the other formulas provide a single value for IBW for a given height over 60 inches. Using the Hamwai formula, the IBW for a male who is 6 ft tall (72 inches) is calculated as 48.1 kg + (2.7 kg x 12 inches/ 60)=80.5 kg or 177 lbs. The hamwi formula yields the highest single-value IBW among all of the formulas in table 8.4. the miller formula provides the lowest IBW, at 73.1 or 161 lbs. if one chooses to use the broca formula, which provides a range, the IBW is 75-91 kg or 165-200 lbs.

lifestyle influences

Diet and physical activity are the most obvious factors that influence energy balance and body weight. Achieving a healthy weight and maintaining an energy balance should be a life-long goal. The most successful approaches include establishing both dietary and exercise habits that improve fitness and lower the risk of disease. For the average person, the importance of controlling the amount of food consumed cannot be overstated. For example, an individual can easily consume 2,000 kcal or more in one meal. In comparison, that same individual would need to walk 21 miles at a brisk pace requiring more than 5 hours to expend 2,000 kcal of energy (see Table 8.3). The importance of food intake in maintaining energy balance is further illustrated by the fact that total energy intake in adults has increased approximately 200-300 kcal/day since the 1970s, which closely parallels the increase in obesity as depicted in Figure 8.6. Daily physical activity and exercise contribute to total expenditure and help maintain energy balance. Unfortunately, nearly half of adults in the United States are physically inactive. In the past 50 years, energy expenditure related to occupations and household activities has declined, thus increasing the importance of planning activities that increase the use of skeletal muscle. Many social factors influence eating behaviors and exercise habits. Research has shown that increased food and energy intake occurs when eating away from home, and people tend to eat more when presented with larger portion sizes. Interestingly, though, there is little evidence that portion size per se is associated with body weight gain. Living in a socioeconomically deprived area, having limited access to supermarkets, and having greater access to fast-food outlets are associated with higher BMI, but whether these factors directly cause body weight gain is unclear. At present, there are relatively few studies that address the impact of social and behavioral factors on food intake, physical activity, and obesity.

leptin

Discovery in 1994 was a milestone event in understanding the relationships between appetite control and obesity. For many years it was suspected that factors in the bloodstream regulated food intake and energy expenditure, and the discovery of leptin provided the first solid evidence. Leptin is a hormone secreted by white adipose tissue that interacts with the hypothalamus to reduce hunger. When leptin binds to its receptors, the orexigenic neurons are inhibited and the production of NPY and AgRP declines, while the anorexigenic neurons are stimulated and release POMC peptides. Leptin levels in the circulation are directly correlated with the amount of body fat. As the amount of body fat increases, so does the level of leptin, thus suppressing hunger. In contrast, less body fat and lower leptin levels mean hunger is suppressed to a lesser extent. The correlation between BMI and leptin concentration is 0.9, illustrating the important role of leptin in the long-term control of body weight. Moreover, mutations in the genes that code for leptin or leptin receptors result in severe obesity the small number of obese individuals in the population who lack leptin because of genetic mutations benefit from leptin injections. On the other hand, the vast majority of obese people have normal or increased leptin levels, but the feeling of hunger persists and they do not decrease food intake. This has given rise to the concept of leptin resistance in which increased leptin levels fail to bring about weight loss even though the leptin receptor is functional. The mechanism of this resistance is not fully understood. One hypothesis is that part of the resistance is due to the inability of leptin to reach the receptor because of diminished transport across the blood-brain barrier. Another hypothesis points to receptor overstimulation, and thus activation of negative feedback pathways that block leptin signaling. The precise mechanisms of leptin resistance require further study. Leptin also exerts rapid effects on glucose and lipid metabolism by activating leptin-responsive relays that are initiated in the hypothalamus and transmitted to other tissues via the sympathetic nervous system. The major tissues affected include the pancreas, skeletal muscle, liver, and adipose tissue. Furthermore, leptin receptors are present in tissues other than the hypothalamus, so leptin can exert direct effects on these tissues independent of its role in the hypothalamus. In skeletal muscle, leptin activates AMP-activated protein kinase (AMPK) and thus promotes fatty acid oxidation and utilization for energy. when AMPK is active (phosphorylated), fatty acid oxidation is stimulated and fatty acid synthesis is inhibited. Direct binding of leptin to tissues also regulates glucose metabolism through its effects on insulin. Leptin inhibits the synthesis and secretion of insulin by the pancreas, while insulin signaling is suppressed in the liver and white and brown adipose tissue.

dual-energy X-ray absorptiometry

Dual-energy X-ray absorptiometry (abbreviated DXA or DEXA) involves scanning subjects with X-rays at two different energy levels, illustrated in Figure 8.11. The subject lies on a table while an X-ray source beneath the table and the detector above the table pass across the subject's body. The attenuation of the beam of X-rays as it passes through the body is calculated by computer. Percentage of fat mass, bonefree fat-free mass, and bone mineral (total body or specific sites) can be calculated based on the restriction in the flux of the X-rays across the fat and the fat-free masses. DEXA is considered to be the gold standard technique for diagnosing osteoporosis and osteopenia and is a commonly used method for body composition measurements. It is widely available and entails relatively low X-ray exposure: 1-10% that of a chest X-ray [19]. Limitations to the use of absorptiometry include the expense of the equipment and the exposure of subjects to radiation. In addition, trained personnel are required to run the instrument and analyze the scans. DEXA measurements are highly reproducible and correlate with other body composition assessment methods. The technique, however, is not accurate for people with metal implants.

weight loss method

Each year many people "go on diets" for the purpose of losing body fat. Depending on the nature of the caloric restriction and the level and type of exercise, both body fat and fat-free mass may be lost. Limited information is available on the proportion of fat and muscle lost on different weight-loss regimes. Losing body fat requires a negative energy balance over an extended period of time. In a systematic review of weight-loss programs lasting at least a systematic review of weight-loss programs lasting at least 6 months, the authors concluded that moderate weight loss (5-10 kg) that consists of both fat mass and fat-free mass can be achieved by calorie restriction alone. Exercise alone is generally considered to be less effective than calorie restriction with exercise. If exercise is added to the weight-loss program, some or all of the fat-free mass can be spared. Most studies have used an aerobic exercise component, and in those that combined calorie restriction with exercise, most of the weight lost was fat mass and very little (0-1.5 kg) was fat-free mass. Resistance training results in only small losses or even a gain in fat-free mass. Research has also explored the relationship between diet composition and weight loss. Some controversy remains as to the proper combination of low fat, low carbohydrate, and/or high protein. However, it appears the most important factor in successful weight loss is the intensity of behavior modification, irrespective of the macronutrient composition of the energy restrictive diet.

measuring body composition

Early observations linking bodyweight with disease risk and mortality, as discussed in previous sections, led to the obvious conclusion that excessive body weight was due to the accumulation of body fat. Humans have a tremendous capacity to store TAGs in adipose tissue when in positive energy balance over time. However, using body weight as a proxy for body fat is less accurate at intermediate body weights because of individuals who gain muscle mass rather than body fat. The desire to have a more complete and accurate understanding of body composition prompted the development of methods that directly assess body fat and other components that include bone, muscle, visceral organs, minerals, and water. Assessment of body composition can be approached in different ways. Modern techniques allow for detailed analyses that can be performed quickly and accurately. Conceptual models of body composition are currently used that partition the body into "compartments." The two-compartment model includes fat mass and fat-free mass, whereas the four-compartment model includes fat mass, fat-free mass, bone mineral, and total body water. The four-compartment model is considered the gold standard but requires sophisticated equipment to measure all of the components. In some cases, the mass of specific organs and the location of adipose tissue can be determined. The most frequently used methods to assess body composition consider only two compartments, fat mass and fat-free mass. Fat mass consists mostly of TAGs, with relatively small amounts of water and minerals. Fat-free mass is much more diverse and comprised of muscle, bones, and the intra- and extracellular fluids. Muscle itself contains about 73% water. The differences in the chemical and physical properties of the two compartments—which include variations in density, the electrolyte content, the ability to conduct an electrical current, and the X-ray density—form the basis for many of the methods of determining body composition. Choosing a method for measuring body composition depends on the purpose, access to the equipment, the number of individuals to be measured, age, and cost. Some methods can be performed only in a laboratory or clinical setting because of the large equipment involved, whereas some methods use portable equipment and can be used in the field.

disordered eating

Eating disorders (Table 5) other than anorexia nervosa, bulimia nervosa, and binge eating disorder are categorized by the American Psychiatric Association as eating disorders not otherwise specified. The characteristics of those with disordered eating are similar to those of individuals with anorexia nervosa and bulimia nervosa and include fear of being fat, restrained eating, binge eating, purging behavior, and distorted body image; however, people with disordered eating do not meet the criteria for anorexia nervosa or bulimia nervosa (Tables 1 and 3). Disordered eating is likely more common than anorexia and bulimia nervosa, and is seen in both males and females, especially female athletes, where it often exists as part of the female athlete triad.

environmental chemicals

Exposure to certain chemicals may play a role in body fat accumulation. Recent research suggests that a group of endocrine-disrupting chemicals present in the environment, including the diet, may predispose some people to gain body fat despite appropriate levels of food intake and physical activity. These chemicals (aptly named obesogens) interfere with hormone function by binding to hormone receptors and either stimulating or inhibiting the signaling pathway. Obesogens are believed to promote triacylglycerol production and deposition in adipose tissue, as well as disrupting appetite control in the hypothalamus. Some evidence suggests that developmental exposure to obesogens early in life may interfere with epigenetic programming of gene regulation, thus influencing the risk of obesity later in life. Much more research is needed to confirm these findings.

Hormonal Influences

Hunger and satiety control meal-to-meal eating behavior, and both are under the influence of hormones. The main target of these hormones is the hypothalamus, in particular, the arcuate nucleus region and its collection of neurons. There are two distinct populations of neurons in the arcuate nucleus with opposing actions. The first group of neurons express hormone receptors and, upon hormone binding, release orexigenic (appetite-stimulating) peptides that include neuropeptide Y (NPY) and agouti-related peptide (AgRP). The other group of neurons produce anorexigenic (appetite-inhibiting) peptides that belong to the pro-opiomelanocortin (POMC) family. The released peptides act as neurotransmitters and affect other neurons within the hypothalamus and elsewhere in the brain to produce the feeling of either hunger or satiety. The hormonal effects can be thought of as short-term, involving daily fluctuations in appetite, and long-term, which impacts energy balance and body weight over time. The so-called "gut hormones" include ghrelin, cholecystokinin, peptide YY, and glucagon-like peptide-1. Hormones secreted by the pancreas, namely insulin and pancreatic peptide, are often included in the list of gut hormones because of the intimate connection between the pancreas and the gastrointestinal tract. In addition, adipose tissue secretes leptin and adiponectin.

indirect calorimetry

In addition to heat production, metabolic processes also consume oxygen in a quantifiable manner. Therefore, the heat released by metabolic oxidation can be calculated indirectly by measuring the consumption of oxygen. Indirect calorimetry is used most often to assess energy expenditure because the required instrumentation can be portable and, under most conditions, does not interfere with physical activities. The expiration of carbon dioxide is also measured so that the ratio of carbon dioxide produced relative to oxygen consumed (termed the respiratory quotient) can be determined. While carbohydrate and fat are the major fuels used in the body, it is recommended that urinary nitrogen excretion also be measured to account for the contribution of protein oxidation to energy expenditure. Oxygen consumption and carbon dioxide production are measured using either portable equipment (Figure 8.1) that can be placed on a person, enabling collection and analysis of gases while mobile or stationary equipment often referred to as a metabolic cart (Figure 8.2). The relative ease of indirect calorimetry makes it a widely used method in research settings when measured data is desired rather than calculated estimates based on body weight.

insulin resistance

Insulin resistance is generally defined as the inability of target tissues to respond to insulin, causing elevated blood glucose (hyperglycemia). This often leads to the diagnosis of type 2 diabetes. The pancreas may release more insulin in an effort to maintain normal blood glucose levels. Elevated insulin levels confirm the type 2 diabetes diagnosis and distinguish it from type 1 diabetes in which insulin is very low or absent. There is no single cause for type 2 diabetes; however, many studies have identified excess body fat as the most important factor predicting type 2 diabetes, with 90% of type 2 diabetic patients falling into the overweight or obese category. The insensitivity to insulin is primarily seen in muscle and adipose tissue. Within insulin-resistant muscle, insulin loses its ability to stimulate glucose uptake; in adipose tissue, it no longer inhibits free fatty acid release. These observations can explain the elevated blood glucose and free fatty acid levels that accompany insulin resistance. The liver and kidney retain their sensitivity to insulin, and the elevated insulin levels stimulate liver triacylglycerol synthesis using the excess free fatty acids. As a consequence, the assembly and secretion of VLDL increases, resulting in elevated fasting serum triacylglycerol. Triacylglycerol levels in the liver also increase, leading to nonalcoholic fatty liver disease. The kidney responds to the elevated insulin levels by increasing renal sodium retention and decreasing uric acid clearance. This response results in an increased prevalence of essential hypertension and higher plasma uric acid concentrations. Each of these metabolic conditions related to insulin resistance—excess body fat, elevated blood glucose, elevated triacylglycerols, and high blood pressure—are diagnostic criteria (along with low HDL cholesterol) for metabolic syndrome. It is easy to see why metabolic syndrome has been called insulin resistance syndrome and why the measurement of insulin resistance was once considered as a diagnostic criterion. However, no simple test exists to determine who is insulin resistant and who is not. Fasting insulin levels, fasting plasma glucose levels, and triacylglycerol: HDL-C ratios have all been used as indicators for insulin resistance, with varying degrees of success. Considerable evidence demonstrates that if a person loses weight, insulin sensitivity improves. Fortunately, the elevated insulin levels do not prevent weight from being lost. On the contrary, free fatty release from adipocytes is accelerated, so it is vital that positive energy balance be avoided for weight reduction to occur. Interesting to note is that variations in the macronutrient content of isocaloric diets have little effect on insulin sensitivity. One common weight loss strategy is to lower the lipid content of the diet and replace it with carbohydrates. The problem with a low-fat, high-carbohydrate diet for a person with insulin resistance, however, is that the additional carbohydrate requires more insulin to be secreted from the pancreas to maintain glucose homeostasis. If the person is insulin resistant, and the pancreas is functioning properly, insulin levels will be elevated further.

body weight: what should we weight?

Many methods have been employed to quantify body fat but most of them require specialized equipment that is expensive and time-consuming to operate. Using bodyweight as a proxy for body fat is convenient, applicable to most people, and can be used by researchers to collect data in large numbers of subjects. An important caveat, however, should be noted when using only body weight as an indicator of health. Some individuals may increase body weight by adding muscle mass rather than fat, as seen in bodybuilders and many competitive athletes. Comparing body weight to height has become a standard measurement of the most desirable weight from a health standpoint [12]. In an attempt to find the most healthy body weight, insurance companies began compiling data from their policyholders whose body weights (relative to height) were associated with the lowest mortality. Eventually, height-weight tables were developed that showed the most desirable weight from a health standpoint [12]. Health professionals began using these tables in the 1940s for educational purposes for the general public. Data from the tables have also been subjected to regression analysis, resulting in the use of ideal body weight formulas for estimating a person's health status. Although the height-weight tables and ideal body weight formulas are able to convey a general notion of disease and mortality risk, they are limited to the demographic populations on which they are based and require a reference population so that the comparative terms desirable and ideal can apply. Many health experts have abandoned the use of height-weight tables and formulas in favor of body mass index and waist circumference as better indicators of body fat (and thus health status) because the latter measurements do not require a reference population for comparison.

indirect calorimetry measuring the energy expanded in physical activity

Measurement of the energy expended in various physical activities has also been made primarily through indirect calorimetry. The method for measuring gas exchange, however, differs slightly from that used for determining BMR. The subject performing the activity for which energy expenditure is being determined inhales ambient air, which has a constant composition of 20.93% oxygen, 0.03% carbon dioxide, and 78.04% nitrogen. Air exhaled by the subject is collected in a spirometer (a device used to measure respiratory gases) and is analyzed to determine how much less oxygen and how much more carbon dioxide it contains compared with ambient air. The difference in the composition of the inhaled air and the exhaled air reflects the energy release from the body. A lightweight portable spirometer. can be worn during the performance of almost any sort of activity, and thus freedom of movement outside the laboratory is possible. In many laboratories and hospitals, gas exchange is measured using a so-called metabolic cart .

the respiratory quotient (RQ)

Measuring gas exchange in indirect calorimetry provides additional information about the fuel sources used in the body. Carbohydrates, fats, and proteins each required different amounts of O2 to completely oxidize to CO2 and water because of primary differences in their chemical structures. Thus, the ratio of CO2 produced relative to O2 consumed, RQ, is characteristic for each fuel source. CHO RQ= 1.0 Fat RQ= 0.70 Protein RQ= 0.82 An RQ value that falls somewhere between the lowest (0.70) and highest (1.0) value indicates a mixture of fuels were used for energy. Measuring gas exchange over a known period of time provides the necessary data to calculate not only total energy expenditure but also the relative contribution of fuel sources. It is assumed that no proteins are oxidized for energy during short-duration activity. Over longer periods, the amount of protein being oxidized can be estimated from the amount of urinary nitrogen excreted, and the remainder of the metabolic energy must be made up of a combination of carbohydrates and fat. Should the principal fuel source shift from mainly fat to carbohydrate, the RQ correspondingly increases, and a shift from carbohydrate to fat lowers the RQ. Table 8.1 includes the thermal (caloric) equivalents of oxygen consumed at RQ values between 0.70 and 1.0, assuming no contribution of proteins to energy expenditure. The use of RQ to calculate energy expenditure also assumes that gas exchange in the lungs reflects the ratio of oxygen consumption and carbon dioxide production at the cell level.

RQ and energy expenditure

Once the RQ has been computed from oxygen and carbon dioxide exchange, the calculation of energy expenditure is performed using the caloric value of oxygen at different RQ values For example: if under standard conditions for the determination of BMR a person consumed 15.7 L of O2 per hour and expired 12.0 L or CO2, the RQ= 12.0/15.7= 0.7643. Based on table 8.1, the caloric equivalent of 1L of O2 at an RQ of 0.76 cals is 4.751 kcal. Based on the caloric equivalent for O2, calories produced per hour are (O2 consumed p/hr x RQ) 15.7 x 4.751, or 74.6 kcal. If we use 75 kcal/h as the caloric expenditure under basal conditions, the basal energy expenditure for the day would be 75kcal/h x 24 h = ~1800kcal/day. At an RQ of 0.76, fat is supplying almost 81% of energy expanded. Because under ordinary circumstances the contribution of protein to energy metabolism is so small, the oxidation of protein is ignored in the determination of the so-called nonprotein RQ. If a truly accurate RQ is required, a minimal correction can be made by measuring the amount of urinary nitrogen excreted over a specified time period. For every 1 g of nitrogen excreted, about 6 L of oxygen is consumed and 4.8 L of carbon dioxide is produced. The amount of oxygen and carbon dioxide exchanged in the release of energy from protein can then be subtracted from the total amount of measured gaseous exchange.

glucagon-like peptide (GLP-1)

Production of GLP-1 occurs along the entire length of the intestine in proportion to caloric intake. GLP-1 release is delayed in obese individuals, who also have lower circulating GLP-1 levels. GLP-1 stimulates the pancreas to secrete insulin while inhibiting secretion of glucagon. It also reduces gastric emptying and intestinal motility, the latter causing signals Production of GLP-1 occurs along the entire length of the intestine in proportion to caloric intake. GLP-1 release is delayed in obese individuals, who also have lower circulating GLP-1 levels. GLP-1 stimulates the pancreas to secrete insulin while inhibiting secretion of glucagon. It also reduces gastric emptying and intestinal motility, the latter causing signals

Mifflin-St. Jeor Equation

Published in 1990, the Mifflin-St. Jeor equations were developed using indirect calorimetry in normal-weight, overweight, obese, and severely obese individuals to improve the accuracy of RMR measurements in people with excess body fat. The Mifflin-St. Jeor equations are used frequently in clinical settings and can accurately predict RMR within 10% of that measured by indirect calorimetry in both nonobese and obese adults. As with Harris-Benedict estimates, separate Mifflin-St. Jeor equations are used for men and women and require body weight, height, and age as data inputs: Men: RMR, kcal/day = (9.99 x W) + (6.25 x H) - (4.92 x A) + 5 Women: RMR, kcal/day = (9.99 x W) + (6.25 x H) - (4.92 x A) + 161 A 35 yrs old female weighting 125 lbs (56.8 kg), and is 5 ft, 5 inches tall (165.1 cm) would have an RMR of 1339 kcal/day using the Harris-Benedict eq and an RMR of 1266 kcal/day using the Mifflin st eq.

predictive equations for RMR

Several equations have been developed that accurately estimate RMR based on body weight, height, age, and gender. These equations do not require specialized equipment or the expertise needed to conduct calorimetric measurements. Many equations have been developed over the past century, although only a few are commonly used today. In general, predictive equations are convenient and yield reasonably accurate estimates of RMR in a variety of populations. However, predictive equations are more variable in older people and tend to overestimate RMR in people with excess body fat. The following describes a few commonly used equations for adult men and women based on body weight in kilograms (W), height in centimeters (H), and age in years (A).

energy expenditure of physical activity

Skeletal muscle requires significant amounts of energy when physically active. Muscle is also involved in maintaining posture when awake, which requires energy in less obvious ways. The energy expenditure of physical activity is highly variable depending on an individual's activity level. Physical activity typically accounts for about 15-30% of total energy expenditure, but it can be considerably less in a truly sedentary person or much more in a very active person. During physical activity that engages large muscles, energy expenditure can greatly exceed RMR at least for a short time. Such high rates of energy usage cannot be sustained, so the daily average of energy expenditure due to physical activity is usually less than RMR in most people. Physical activity includes all exercise and non-exercise activities associated with daily living. Quantifying the energy expenditure of physical activity requires measuring RMR (or BMR) and total energy expenditure, then calculating the difference. This can be achieved in a clinical setting by measuring gas exchange (oxygen consumed and carbon dioxide expired) or by predictive equations. Alternatively, practitioners can simply estimate the contribution of physical activity to total energy expenditure by a factor that approximates the additional energy usage by skeletal muscle [8]. The multiplication factors— called the physical activity level (PAL)—are categorized into four different levels, as described in Table 8.2. For comparison, Table 8.2 also shows the number of miles a person would need to walk per day to match each PAL category. 125-lb female as an example, we start with her RMR of 1,266 kcal/day that was calculated using the Mifflin-St. Jeor equation. We know she works at a home improvement store and walks throughout the day, putting her in the "active" PAL category. Therefore, the combined energy expenditure attributed to RMR and physical activity is 1,266 x 1.75 = 2,216 kcal/day. Another way of estimating energy expended during physical activity is the use of data tables in which the amount of energy expended has previously been determined for a variety of activities. Table 8.3, an example of such a table, indicates the amount of energy (kcal) expended per minute per body weight. This table incorporates the basal energy expenditure, whereas some tables provide data for only physical activity. To calculate the energy expended for a given activity, multiply the kcal by your body weight and then by the number of minutes spent performing the activity. Note that every activity performed during a 24-hour period (and possibly for several days) would need to be recorded if total daily energy expenditure is desired.

binge eating disorder

The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders includes a provisional eating disorder diagnosis, binge eating disorder, which is not associated with purging as in bulimia nervosa. Binge eating disorder is characterized by binge eating at least twice a week for at least a 6-month period with no compensatory behaviors. The binge eating episode typically involves eating (usually with a general sense of lack of control) large amounts of highly energy-dense foods (such as dessert and snack food-type items) more rapidly than normal and continues despite the individual feeling uncomfortably full. Subtypes of the disorder are mainly distinguished by whether the binge precedes dieting or whether dieting precedes the binge eating. Factors associated with binge eating include repeated exposure to negative comments about eating, shape, and weight; depression; negative self-evaluation; and vulnerability to obesity. For those with a binge eating disorder, food often provides comfort and a sense of emotional well-being, especially if the person is feeling stressed, anxious, unhappy, or depressed. Thus, the binge usually occurs when the person is not physically hungry but is emotionally unhappy. The binge usually happens in private because of embarrassment, and, following the binge, feelings of disgust, guilt, and depression are common.

Pancreatic Polypeptide (PP)

The anorexigenic PP is synthesized primarily in the pancreas and secreted in response to food intake. Its mechanisms of action are not well understood, although PP receptors are present in the hypothalamus and binding appears to downregulate NPY mRNA expression, thus decreasing hunger. PP has a relatively short half-life in the circulation and therefore a brief period of action.

regulation of energy balance and body weight

The concept of energy balance has been discussed throughout this chapter, particularly positive energy balance that promotes body fat accumulation. Although the concept of energy balance could apply to the daily shifts in metabolic fuels that occur during the fed-fast cycle or bouts of exercise (discussed in Chapter 7), most health professionals refer to energy balance within the context of body composition and the changes that may occur over weeks, months, or years. When an individual is in a positive energy balance over time, the excess energy, regardless of the macronutrient form in which it was consumed, will be stored as triacylglycerols in adipose tissue. Most experts generally agree on this concept, as emphasized in the Dietary Guidelines for Americans that recommend eating "within an appropriate calorie level" and engaging in "regular physical activity in a variety of ways" [21]. Even slight imbalances can have a significant long-term impact on body weight. Consuming an energy excess of just 150 kcal per day—the amount found in one 12 oz. soft drink—can result in the gain of one pound of adipose tissue in just 23 days. Although once thought to be a simple matter of "energy in versus energy out," numerous lines of evidence have shown energy balance to be tightly controlled by several hormones working in concert. Additional internal and external factors can influence the function of these hormones and thus food intake, energy expenditure, and body fat deposition.

metabolic syndrome

The definition of syndrome is a clustering of factors that occur together more often than expected based on chance alone, and whose cause is often uncertain. The concept of metabolic syndrome refers to a group of risk factors that are associated with an increased risk of cardiovascular disease (CVD). The risk factors for metabolic syndrome include central obesity; increased fasting plasma glucose; increased fasting plasma triglyceride; decreased plasma HDL cholesterol; and hypertension. A diagnosis of metabolic syndrome requires a patient to exhibit three of the five conditions as defined in Table 8.7. It is believed that the underlying mechanisms uniting these factors are related to insulin resistance. Metabolic syndrome diagnosis holds promise as a predictor of disease: it is associated with a two-fold increase in risk for CVD, myocardial infarction, stroke, and CVD-related mortality [40]. Metabolic syndrome diagnosis is associated with a 1.5-fold increase in the risk of all-cause mortality. Still to be determined, however, is whether a diagnosis of metabolic syndrome is a better predictor of risk than the sum of the individual risk factors. Furthermore, central (android) obesity has consistently been recognized as a key component of the syndrome and is nearly always one of the diagnostic criteria. This has led to considerable debate about the usefulness of metabolic syndrome as a practical clinical tool in identifying patients in need of treatment. In fact, the American Diabetes Association and the European Association for the Study of Diabetes issued a joint statement emphasizing that the risk of CVD associated with metabolic syndrome diagnosis is no greater than the sum of each factor, calling into question the medical value of diagnosing the syndrome. In many cases, a reduction in body weight alone will improve each of the other diagnostic factors.

Laboratory methods; Densitometry: Underwater Weighting

The density of body fat is about 0.9 g/mL, whereas the density of fat-free mass is about 1.1 g/mL. Percent body fat of an individual can therefore be calculated if whole-body density is known. The Greek mathematician Archimedes discovered that the volume of an object submerged in water is equal to the volume of water displaced by the object. The density of an object can then be calculated by dividing the object's weight (wt) in air by its loss of weight in water. For example, for a person who weighs 47 kg in air and 2 kg underwater, 45 kg represents the loss of body weight and the weight of the water displaced. After an adjustment for the change in density of water at different temperatures is made, the volume of the person can be calculated. Figure 8.9 illustrates an apparatus for weighing underwater. Correction for residual air volume in the lungs (RLV) and gas in the gastrointestinal tract (GIGV) must be made. Body density is calculated using the following formula: Body density: weight of body in air/((wt of body in air-wt of body underwater)/ density of water)- RLV-GIGV Residual lung volume is thought to be about 24% of vital lung capacity. The volume of gas in the gastrointestinal tract is estimated to range from 50 to 300 mL. This volume typically is neglected, or a value of 100 mL may be used in calculations. The density or the weight of water is known for a wide range of temperatures and must be obtained for the calculation. Once the density of the human body is known, an estimation of body fat can be determined. At any known body density, estimating the percentage of body fat is possible using established equations. Underwater weighing is considered a noninvasive and relatively precise method for the assessment of percent body fat. The standard error of body fat measurements using densitometry has been estimated at 2.7% for adults and about 4.5% for children and adolescents. Measurements obtained by underwater weighing correlate well in broad populations with those obtained by other techniques. Limitations of underwater weighing include its relatively high equipment cost, the inability to measure gas volume in the gastrointestinal tract, its impracticality for large numbers of subjects, and the high level of cooperation and time required of subjects, who must be submerged and remain motionless for an extended time. Thus, the technique is not suitable for young children, older adults, or subjects in poor health.

doubly labeled water

The doubly labeled water method also enables the assessment of total energy expenditure. 2H2 (deuterium) and 18O2 are stable isotopes of hydrogen and oxygen, respectively. In this technique, stable isotopes of water are given (for subject to drink) as H2 18O2 and as 2H2O (or as 2H2 18O2). The isotopes equilibrate throughout the water compartments in the body over about 5 hours. The labeled hydrogen can leave the body as water (2H2O) in sweat, urine, and pulmonary water vapor, while the labeled oxygen can leave the body as either labeled water (H2 18O) or C18 O2. The disappearance of the H O2 18 and 2H O2 is measured in the blood and urine for about 3 weeks. The disappearance of the H2 18O2 is representative of the flux of water (i.e., water turnover) and of the production rate of carbon dioxide. Because the 2H2 can be excreted only as H O2, the disappearance of the 2H O2 represents water turnover alone. Thus, the difference between the disappearance rate of H O2 18 and that of 2H. The CO2 production rate is then used to calculate energy expenditure. However, an RQ is needed to determine the caloric value of CO2 using Table 8.1. Rather than measuring gas exchange, which would defeat the unrestricted character of the doubly labeled water technique, food records are kept throughout the testing period to estimate the metabolic fuel mix from dietary intake. In subjects maintaining body weight, the recorded food quotient is equal to the respiratory quotient and can act as a surrogate RQ. The use of the doubly labeled water method to assess total energy expenditure in free-living individuals produces accurate results that correlate well with those of indirect calorimetry. One source of potential error lies with the use of food records, which requires attention to detail and knowledge of portion size to improve accuracy.

the female athlete triad

The female athlete triad, first described in 1992 and defined as the combination of disordered eating, amenorrhea, and osteopenia, is described as a complex interrelationship between menstrual status, bone health, and energy availability. The condition appears most often in women participating in sports in which physique and body image are important and extra body weight is undesirable. While all-female athletes are considered at risk, women most at risk include long-distance runners, figure skaters, gymnasts, ballet dancers, swimmers, and divers. Inadequate energy intakes among athletes may be related to disordered eating—with an estimated prevalence of 10-20% in athletes—or simply to a failure to meet the high energy needs of the sport (unassociated with disordered eating). The causes of amenorrhea in athletes, as in women with eating disorders, are not clearly understood. They are thought to relate to synergistic effects of excessive amounts of physical activity and training, constant stress or anxiety, low amounts of body fat, weight fluctuations, and poor diet, especially an extreme energy (caloric) deficit. The effect of these various factors is to evoke changes in the release of hormones such as follicular stimulating and luteinizing hormones that then lead to diminished release of estrogen and progesterone (among other hormones), which in turn can cause amenorrhea. The amenorrhea—more specifically, the diminished serum estrogen concentrations—in turn negatively impact the skeletal system, similar to what is observed in those with anorexia nervosa. Premature bone loss, inadequate bone formation, or both with resulting low bone mass, stress fractures, and other orthopedic problems are common among female athletes; in fact, over 50% of athletes with amenorrhea have low bone mass or bone densities at least one standard deviation below the mean. High levels of cortisol in the blood, common in athletes, and extensive training regimens also can contribute to bone loss along with poor energy and nutrient (especially vitamin D and calcium) intakes. Some of the American College of Sports Medicine's recommendations for the prevention and treatment of the female athlete triad emphasizes optimizing energy and nutrient availability and providing medications, as needed, to improve bone health and for psychological problems, although the full reversal of low bone mineral density is thought to be unlikely.

intestinal microbiota

The human gastrointestinal tract is host to trillions of microbial cells that participate in nutrient digestion and utilization. Growing evidence indicates that intestinal microbiota are also linked to obesity development and metabolic dysfunction. Normally the microbial community is dominated by bacteria, with 90% belonging to the phyla Firmicutes and Bacteroidetes. In obese people, the intestinal microbiota is altered and responds to changes in body weight. Excess body fat is associated with more Firmicutes and fewer Bacteroidetes. The level of Bacteroidetes increases when weight is reduced with energy-restricted diets, although it is unclear whether the microbiota are responding to changes in energy intake or changes in adiposity. One possible outcome of altered microbiota is their altered ability to ferment non-digestible carbohydrates (fiber) and produce short-chain fatty acids. The microbiota of obese individuals have an increased capacity to ferment fiber and thus "harvest" more energy as short-chain fatty acids that contribute to the total energy absorbed into the body. The additional energy can be stored as body fat. The short-chain fatty acids may also act as signaling molecules in intestinal cells by decreasing the production of the anorexigenic hormones, GLP-1 and PYY, thus removing the feeling of satiety. Long-term dietary habits have a significant impact on intestinal microbiota, as evident in populations that consume different macronutrient profiles. For example, the microbiota resulting from European diets rich in protein and animal fat are quite different compared to high-fiber diets in West Africa, which are rich in cellulose and hemicelluloses. The microbiota in West Africans have adapted to fermenting these fibers to gain maximum energy as short-chain fatty acids. The interrelationships of intestinal microbiota, diet, and obesity are complex and difficult to study because of the high degree of variability in human microbiota and diet. Nevertheless, it has been established that an individual's diet is a strong determinant of the microbiota composition and that altered microbiota profiles are associated with obesity.

peptide YY (PYY)

The small and large intestine produces PYY and its action lasts longer than the other anorexigenic hormones. This characteristic is important in countering the effects of CCK by inhibiting intestinal motility and secretion of digestive juices. In addition, PYY binds to receptors in the hypothalamus, although the anorexigenic mechanisms of action are not fully understood. Circulating levels of PYY are lower in obese individuals.

health implications of altered body weight

The terms overweight and obesity are often used to indicate different degrees of body "fatness." The overweight category, as previously mentioned in this chapter, can unintentionally include individuals who have gained muscle mass rather than fat. The obesity category, on the other hand, includes only those with excess body fat. Accumulation of body fat is associated with an increased risk of mortality and morbidity due to hypertension, stroke, coronary artery disease, dyslipidemia, type 2 diabetes, sleep apnea, osteoarthritis, and certain cancers. During the past 50 years, the prevalence of overweight and obesity has risen steadily to epidemic levels (see Figure 8.6). Currently, in the United States, there are 79 million obese adults, projected to increase to 144 million by 2030 with an additional economic burden of $48 billion to $66 billion per year. When assessing the health risks related to excess body fat, the differences in fat distribution between men and women should be considered. Recall from Chapter 6 the concept of the reference man and woman (Table 6.8) in which women have significantly more "essential fat," referring to the subcutaneous fat that accumulates mostly around the hips and thighs and in mammary tissue. On the other hand, excess fat in both men and women can accumulate within the body core (visceral fat) and subcutaneously around the torso. These observations form the basis of definitions for two patterns of obesity. Gynoid obesity, also called pear-shaped, is associated primarily with women and refers to the excess fat that accumulates around the hips and thighs. Android obesity, or apple-shape, describes the central adiposity resulting from the accumulation of excess visceral fat. Android obesity is more strongly associated with disease risk. Consequently, measuring waist circumference or waist-to-hip ratio is a more useful risk assessment tool than body weight or BMI alone. At the cell level, the deposition of triacylglycerols causes adipocytes to become enlarged (hypertrophy). In addition, new adipocytes can be produced (hyperplasia) to accommodate more triacylglycerol molecules. The creation of new fat cells increases most rapidly in late childhood and early puberty whenever a positive energy balance exists, although hyperplasia can occur later in life as well. Obese people have more, and larger, fat cells than nonobese people. If body fat is lost, the number of fat cells does not decrease; they just get smaller.

Skinfold thickness; field methods

The use of skinfold measurements as an indicator of body fat is based on the assumption that the thickness of subcutaneous fat directly correlates with total body fat. Skinfold measurements can estimate the percentage of body fat and is therefore consistent with the two-compartment model. Skinfold measurements are made at various anatomical sites using a caliper (Figure 8.7). The anatomical sites commonly used for measuring skinfold thickness are the triceps (measured on the back of the upper arm), subscapula (measured just below the tip of the scapula), suprailiac (measured above the hip bone), abdomen (measured 1 inch to the right of the umbilicus), and thigh (measured at the midpoint of the thigh, between the kneecap and the hip). All measurements should be repeated at least two or three times, and the average should be used as the skinfold value. The precision of skinfold thickness measurements depends on the skill of the technician; in general, a precision of within 5% can be obtained by a well-trained and experienced technician. After skinfold thickness is measured, the values are entered into mathematical equations to calculate the percentage of body fat. Because of the convenience and low cost, the use of skinfold measurements is a popular choice of community-based health and wellness practitioners.

Energy expended on various activities Table 8.3

The values listed in this table reflect both the energy expended in physical activity and the amount used for BMR. To Calculate kcal spent per minute of activity for your own body weight, multiply kcal/lb/min (or kcal/kg/min) by your exact weight and then multiply by the number of minutes spent in the activity. (kcal/lb/min x weight x minutes spent) For example, if you weigh 142 pounds, and you want to know how many kcal you spent doing 30 minutes of vigorous aerobic dance: 0.062 x 142= 8.8 kcal per minute; 8.8 x 30 minutes = 264 total kcal spent.

weight-only equations

These equations are less accurate but work reasonably well when information about height or age is unavailable. Perhaps the most frequently used weight-only equation is not based on established gas exchange methodology, but rather on the principle that basal metabolic rate (represented by heat production) is correlated with a body mass of most vertebrate animal species. The resulting equation for humans is specific for BMR and is written: BMR, kcal/day 7 5 30 W0.75 Using the same 125-lb (56.8-kg) female as an example, her estimated BMR is calculated to be 70 x 56.8^0.75 = 1,448 kcal/day.

adiponectin

adipocyte-derived hormone that plays a role in energy homeostasis. Plasma adiponectin levels are negatively correlated with body fat. Circulating levels of adiponectin are low in obese individuals but increase in response to weight loss. Receptors for adiponectin are located in the hypothalamus, skeletal muscle, liver, and smooth muscle of the cardiovascular system. Although the precise role of adiponectin is not fully understood, plasma levels are inversely correlated with a number of metabolic conditions that include hypertension, type 2 diabetes, plasma triacylglycerol concentration, body mass index, several inflammatory markers, bone mineral density, and the risk of some cancers. The promise of adiponectin as a protective molecule against inflammation, atherosclerosis, diabetes, and cancer has led to dietary and lifestyle strategies that boost the levels of plasma adiponectin levels. Caloric restrictive diets and associated weight loss increase adiponectin, as does the consumption of n-3 fatty acids, monounsaturated fatty acids, garlic, and the Mediterranean diet. Exercise contributes to the beneficial effect of adiponectin by increasing the number of adiponectin receptors.

insulin

insulin suppresses hunger through its action on orexigenic and anorexigenic neurons, although its effects are less robust than leptin. Insulin receptors are distributed throughout the brain, with high concentrations in the arcuate nucleus. Insulin binding stimulates the release of POMC peptides and inhibits the release of NPY and AgRP. Also similar to leptin, blood insulin levels increase in proportion to body fat, which may be the result of insulin resistance. Previous chapters highlighted the role of insulin in anabolic metabolism and energy storage through its direct action in several peripheral tissues such as muscle, adipose tissue, and liver. Insulin binding to hypothalamic receptors also transmits signals to peripheral tissues, which inhibits gluconeogenesis and proteolysis in the liver and stimulates lipogenesis and triacylglycerol accumulation in adipose tissue. The deposition of triacylglycerols, in turn, stimulates the release of leptin by adipocytes. This metabolic coordination of insulin and leptin is not fully understood, although their action clearly impacts long-term energy homeostasis beyond just daily appetite control.

direct calorimetry

metabolic processes in the body result in the production of health. Metabolic oxidation of a typical FA releases more energy as heat than is captured in ATP molecules. Consequently, energy expenditure can be quantified by measuring heat dissipated by the body. The technique of direct calorimetry is highly accurate and includes both sensible heat loss and heat of water vaporization. Although the concept of direct calorimetry is relatively simple, direct measurement of body heat loss is expensive, impractical, cumbersome, and usually rather unpleasant for the subject or subjects involved. Direct calorimetry is seldom used and has been replaced by the indirect methods

ghrelin

produced predominantly in the stomach and, unlikely the other regulatory hormones, stimulates the feeling of hunger. Ghrelin secretion rises between meals when the stomach is empty. It binds to receptors in the orexigenic neurons of the hypothalamus, causing the release of NPY and AgRP. As a meal is consumed and nutrient absorption begins, ghrelin secretion rapidly diminishes and hunger reduces. The half-life of ghrelin in the serum is only about 30 minutes. However, in obese individuals, the postprandial decline in ghrelin does not occur and may contribute to overeating. Ghrelin also promotes digestion by stimulating gastric acid secretion and gastric motility prior to food consumption.

basal energy expenditure

the energy expended to maintain an awake resting body that is not digesting food

positive energy balance

the state in which energy intake is greater than energy expended, generally resulting in weight gain. A person who habitually consumes energy in excess of energy needs is in positive energy balance and will convert unused energy into TAGs for storage as body fat.

energy balance

when the amount of food energy matches energy expenditure over time