L7: regulation of eating

obesity health problems

1) CV: hyperlipidemia, HTN, obstructive sleep apnea 2) diabetes 3) gallbladder

leptin effects

1) decreased production of Neupropeptide Y and AGRP: suppress appetite 2) activation of POMC neurons, causing release of α-MSH and activation of melanocortin receptors 3) increased production in the hypothalamus of corticotropin-releasing hormone, decrease food intake 4) increased sympathetic nerve activity, which increases metabolic rate and energy expenditure 5) decreased insulin secretion by pancrease, which decreases energy storage

obesity treatments

1) diet 2) exercise 3) medicine: amphetamines, sibutramine (sympathomimetic), fat absorption blockers (orlistat), carbohydrate absorption blockers 4) psychological counseling 5) surgery: bypass, banding

causes of obesity

1) energy intake > energy output 2) decreased PE, sedentary lifestyle 3) abnormal feeding regulation: childhood overeating 4) genetic: altered set point, fat chemistry (20-25% of cases) 5) environmental factors 6) psychological factors 7) neurogenic factors

hunger factors

1) habit: meal schedule 2) presence of appetizing food: appearance, odor, taste, texture, temperature 3) other people eating 4) ghrelin 5) signals to the brain that supply of nutrients is low in protein, glucose, FA (protein and carbohydrate stores are relatively constant, adipose stores may change markedly in adults).

neurogenic causes of obesity

1) morbid obesity: hypothalamic or brainstem tumors/lesions (rare) 2) functional reorganization of brain centers: more likely 3) abnormality of NT or receptor mechanisms in neural pathways

obesity

50-60% of population is overweight, with a BMI between 25-29.9. an individual is considered obese when weight is 20% (25% in women) or more over the max desirable for their height: BMI greater than 30; this accounts for 30% of the population. when an adults is more than 100 lbs overweight, its considered morbidly obese (BMI over 40); this accounts for 10% of the population.

glucostatic theory

An increase in blood glucose level increases the rate of firing of glucoreceptor neurons in the satiety center in the ventromedial and paraventricular nuclei of the hypothalamus. The same rise in blood glucose level simultaneously decreases firing of neurons called glucosensitive neurons in the hunger center of the lateral hypothalamus. it also goes the other way, low blood glucose levels stimulate the hunger center and inhibits the satiety center. this is due to insulin dependent, glucose sensitive neurons (glucostats) in the hypothalamus. In addition, amino acids and lipid substances affect the firing rates of these same neurons or other closely associated neurons (aminostatic and lipostatic theories).

hormonal suppression of feeding

CKK, glucagon, somatostatin, bombesin (gastrin releasing peptide), leptin. effects last 2 hours.

leptin obesity

In mice with mutations that render their fat cells unable to produce leptin or that cause defective leptin receptors in the hypothalamus, marked hyperphagia and morbid obesity occur. However, there does not appear to be a deficiency of leptin production in most obese humans, because plasma leptin levels increase in proportion with increasing adiposity. Therefore, some scientists believe that leptin receptors or post-receptor signaling pathways normally activated by leptin may be defective in obese people, who continue to eat despite very high levels of leptin. Another explanation for the failure of leptin to prevent increasing adiposity in obese individuals is that there are many redundant systems that control feeding behavior, as well as sociocultural factors that can cause continued excess food intake even in the presence of high levels of leptin.

childhood overeating

Rate of formation of new fat cells is especially rapid in the first few years of life, and the greater the rate of fat storage, the greater the number of fat cells. The number of fat cells in obese children is often as much as three times that in normal children. However, after adolescence, the number of fat cells remains almost constant throughout the remainder of life. Therefore, it has been suggested that overnutrition of children, especially in infancy and to a lesser extent during the later years of childhood, can lead to a lifetime of obesity.

oral receptors

When an animal with an esophageal fistula is fed large quantities of food, even though this food is immediately lost again to the exterior, the degree of hunger is decreased after a reasonable quantity of food has passed through the mouth. This effect occurs despite the fact that the GI tract does not become the least bit filled. Therefore, it is postulated that various "oral factors" related to feeding, such as chewing, salivation, swallowing, and tasting, "meter" the food as it passes through the mouth, and after a certain amount has passed, the hypothalamic feeding center becomes inhibited. However, the inhibition caused by this metering mechanism is considerably less intense and shorter lasting, usually lasting for only 20 to 40 minutes, than is the inhibition caused by gastrointestinal filling.

leptin

a peptide hormone that is released from white adipocytes and is used by the hypothalamus to sense fat stores. when amounts of adipose increase, they increase the amounts of leptin, which is released into blood. leptin crosses the BBB via facilitated diffusion and occupies receptors at multiple sites in the hypothalamus, especially the arcuate and paraventricular nuclei. stimulation of these receptors initiates multiple actions that decrease fat storage.

AGRP

acts as an antagonist of MCR4. insulin, leptin, and CKK inhibit AGRP-NPY neurons and stimulate adjacent POMC-CART neurons, thereby reducing food intake

prefrontal cortex

also cortical areas of the limbic system. these areas are responsible for determining the quality of food that is ingested. it remembers previous unpleasant experiences (food poisoning).

regulation of adiposity: set point/range theory

any change in adiposity (not weight) is compared with an internally set standard for adiposity. the feedback response is relative to the deviation from this set point, and will elicit proportional metabolic or behavioral responses opposing the deviation from the set point. weight can and will deviate within an acceptable range above or below the usual weight. maintenance of weight within this acceptable range can be controlled by dietary habits, short term (meal-to-meal) regulation, or both. deviation of weight outside this acceptable range would initiate more potent, long term regulatory systems. this body weight set point/range changes readily with changes in physical activity, dietary composition, emotional state, stress, and pregnancy (it is not strictly controlled).

anorexia

aversion to eating. may be due to a psychological or pathological abnormality. can be defined as a reduction in food intake caused primarily by diminished appetite, as opposed to the literal definition of "not eating." This definition emphasizes the important role of central neural mechanisms in the pathophysiology of anorexia in diseases such as cancer, when other common problems, such as pain and nausea, may also cause a person to consume less food

adipose feedback signals

body fat, especially triglyceride, stores are regulated variably and any deviation results in changes in feeding behavior. hypothalamic receptors monitor and regulate circulating levels of fat metabolites (fatty acids, glycerol, 3-hydroxybutyrate) which signal the size of body fat stores. increases or decreases in size of fat stores results in compensatory hypo or hyperphagia and change in metabolic rate to restore body fat stores to normal sizes.

appetite

complex. is a desire for a particular type of food and is useful in helping to choose the quality of the food to be eaten. If the quest for food is successful, the feeling of satiety occurs. Environmental and cultural factors as well as specific centers of the brain, especially the hypothalamus, influence each of these feelings. includes the desire to eat even when hunger has been appeased.

brainstem

controls the mechanics of feeding: salivation, licking lips, chewing, swallowing

hypothalamus

controls the quantity of food intake and excites the lower centers to activity. it receives neural signals from the GI tract regarding sensory information about stomach filling, chemical signals from nutrients in blood (glucose, AA, FA) that signify satiety, signals from GI hormones released by adipose tissue, and signals from the cerebral cortex (sight, smell, taste) that influence feeding behavior. much chemical cross talk occurs among the neurons on the hypothalamus, and together these centers coordinate the processes that control eating behavior and the perception of satiety. these hypothalamic nuclei also influence the secretion of several hormones that are important in regulating energy balance and metabolism, including those from the thyroid and adrenal glands, as well as the pancreatic islet cells.

hunger

craving for food: objective or physiological awareness of the need to ingest food. Sensation of hunger is associated with several objective sensations, such as rhythmical contractions of the stomach, malaise, and restlessness that cause the person to search for an adequate food supply. subjective sensations are due to low levels of nutrients in blood.

eating

feedback system of physiologically complex, motivated behaviors. should be adequate to meet metabolic needs of tissues. it is influenced by physiological, emotional, environmental, cultural, and genetic factors. eating is initiated in response to hunger sensations (continues while total quantity and specific nourishment of ingested food is monitored). repletion of nutrients causes satiation.

ghrelin

hormone secreted from the stomach, primarily from parietal cells in the fundus, and the small intestine (minor amounts from kidney, pituitary, others). its release is stimulated by decreased energy stores and it in turn activates AGRP-NPY neurons and stimulates food intake. levels increase before a meal (not a catalyst to hunger, but a meal initiation signal). gastric bypass surgery reduces levels. levels fall rapidly after food intake.

lateral nuclei hypothalamus

hunger or feeding center. stimulation of this area causes an animal to eat voraciously (hyperphagia). destruction causes lack of desire for food and progressive inanition (weight loss, muscle weakness, decreased metabolism). it operates by exciting the emotional and motor drives of the animal to search for food and controls the amount eaten. it excites brainstem centers controlling chewing, salivation, and swallowing. its tonically active, inhibited by stimulation of the satiety center.

lipostatic theory

increasing plasma fatty acid levels while eating stimulates the satiety center. this hypothesis is supported by discovery of LH neurons that are sensitive to the application of free fatty acids. it is the least potent satiating nutrient despite CKK release.

GI filling

inhibits feeding. Distension of gastrointestinal tract, especially the stomach and the duodenum → stretch inhibitory signals transmitted mainly by way of the vagi to suppress feeding center, thereby reducing desire for food. effects last 1-2 hours.

cachexia

is a metabolic disorder of increased energy expenditure leading to weight loss greater than that caused by reduced food intake alone. Anorexia and cachexia often occur together in many types of cancer or in the "wasting syndrome" observed in patients with acquired immunodeficiency syndrome (AIDS) and chronic inflammatory disorders. Almost all types of cancer cause both anorexia and cachexia, and anorexia-cachexia syndrome develops in more than half of persons with cancer during the course of their disease.

anorexia nervosa

is an abnormal psychic state in which a person loses all desire for food and even becomes nauseated by food; as a result, severe inanition occurs.

inanition

is the opposite of obesity and is characterized by extreme weight loss, muscle weakness, and decreased metabolism. It can be caused by inadequate availability of food or by pathophysiological conditions that greatly decrease the desire for food, including psychogenic disturbances, hypothalamic abnormalities, and factors released from peripheral tissues. In many instances, especially in persons with serious diseases such as cancer, the reduced desire for food may be associated with increased energy expenditure, resulting in serious weight loss.

paraventricular nuclei hypothalamus

lesions cause excessive eating

dorsomedial nuclei hypothalamus

lesions usually depress eating behavior

amino static (protein) theory

levels of AA precursors (tryptophan, tyrosine, choline) can affect formation of their respective products such as serotonin, catecholamines, and acetylcholine. these NT may be critical to central regulation of feeding and satiety. very potent satiating nutrient.

long term regulation

maintenance of normal quantities of energy stores in the body: 1) blood concentrations of glucose, AA, lipids 2) temperature regulation 3) feedback signals from adipose tissue.

NPY-AGRP neurons

neuropeptide Y & agouti-related protein. activation increases food intake and reduces energy expenditure.

bulemia

normal or over-intake of food (binging) followed by purging. patient may also abuse laxatives, emetics. requires psychotherapy. 50% never cured. medical problems include: GI, CV, dental, and electrolytes.

amygdala

portions of the amygdala are a major part of the olfactory nervous system. destructive lesions have demonstrated that some of its areas increase feeding, whereas other areas inhibit feeding. in addition, stimulation of some areas elicit the mechanical act of feeding. bilateral destruction of the amygdala results in a psychic blindness in the choice of foods. the animal loses or at least partially loses the appetite control that determines the type and quality of food it eats.

satiety

postprandial levels that affect the interval to the next meal, regulating meal frequency. the amount of food causing satiety depends, in part, on whether the energy stores are full: nutritional satisfaction. this is influenced by learned habits

short term regulation

prevents overeating at each meal: 1) GI filling/stretching 2) GI hormones (CKK, PYY, GLP) 3) ghrelin 4) oral receptors

satiation

processes that promote meal termination, limiting meal size. it is the opposite of hunger. it is the feeling of fulfillment in the quest for food resulting from ingestion of a meal in a normal individual.

pro-opiomelanocortin (POMC) neurons

produce alpha-melanocyte stimulating hormone (alpha-MSH) together with cocaine and amphetamine related (CART). activation of POMC decreases food intake and increases energy expenditure.

alpha-MSH

released by POMC and stimulates melanocortin receptors MCR3 & MCR4 in the paraventricular nuclei, which then activate neuronal pathways that project tot he nucleus tractus solitarius and increases sympathetic activity and energy expenditure.

ventromedial nuclei hypothalamus

satiety center. gives a sense of nutritional satisfaction that inhibits the feeding center. electrical stimulation can cause complete satiety, and even in the presence of highly appetizing food, the animal refuses to eat (aphagia). destruction can cause voracious and continued eating until the animal becomes extremely obese, sometimes as large as four times normal.

arcuate nuclei hypothalamus

the sites in the hypothalamus where multiple hormones released from the GI tract and adipose tissue converge to regulate food intake, as well as energy expenditure. two distinct types of neurons are important as controllers of both appetite and energy expenditure: pro-opiomelanocortin (POMC) neurons and neurons that produce orexigenic substances NPY and AGRP. these are the major targets for several hormones that regulate appetite: leptin, insulin, CKK, ghrelin. neurons of the arcuate nuclei appear to be a site of convergence of many of the nervous and peripheral signals that regulate energy stores.

body temperature & food intake

when an animal is exposed to cold, it tends to over eat, which increase its metabolic rate and provides increased fat for insulation, both of which tend to correct the cold state. when an animal is exposed to heat, it tends to under eat. this is caused by the interaction within the hypothalamus between the temperature regulating system and the food intake regulating system.