Glucose Metabolism and Obesity
How can obesity be defined with its most reliable measurement?
BMI (Body Mass Index) is > or = 30 kg/m^2
What ethnic groups are at higher risk than Caucasians for metabolic syndrome?
Hispanic Americans
What is an FDA approved APPETITE SUPPRESSANT?
Lorcaserin hydrochloride
What is chronic, low grade inflammatory state in obesity linked to?
Metabolic dysfunction
What are METABOLIC CHANGES in OBESITY due to?
Molecular signals originating from increased adipocyte mass (adipokines)
What is the "THRIFTY GENE" THEORY?
Individuals obese in the past may have been more efficient in storage of energy during times of feast and better to survive times of famine SO genetic tendency to accumulate fat is left over from days of high activity and scarce food sources (in past)
What appetite hormone is insulin sensitizing? What does that mean and what that implies? What happens during obesity?
- Adiponectin - It makes insulin work better and therefore it is good for decreasing circulating fatty acids and glycemic control for diabetics - It is decreased
Does GYNOID or ANDROID body fat distribution give higher risk? What is higher in risk (related to blood pressure, glucosex2 and artery)?
- Android (upper body fat and apple shaped) - Increased risk of hypertension, insulin resistance, diabetes, coronary artery disease
What is considered an unfit lean man? What is related to their risk compared to fit men with BMI > 27.8?
- BMI < 25 - 2x risk of mortality from all causes
What is surgery for weight loss and major concern?
- Bariatric surgery - It is MAJOR SURGERY and 1 in 200 people die
What type of patients may have higher risk of metabolic syndrome with simply marginally increased waist size? What is that waist size?
- Genetically predisposed patients to insulin resistance - MALES 37 - 39 inches and FEMALES 31 to 35 inches
What type of obesity has NORMAL METABOLIC PROFILE? Why?
- Subcutaneous obesity - There are no ectopic fat deposits in other parts of the body
There is poor _____ and ____ that causes "drive to ____"
- regulation of appetite - satiety - overeat
With LIMITED OBESITY, the adipose tissue should have _____ (metabolic function, immune cell activation, vascular function)
- relatively normal metabolic function - low immune cell activation - sufficient vascular function
Obesity is a _____ and has surpassed _____ as a public health issue
- rising epidemic - malnutrition
Obesity is a _____ medical condition requiring _____ management
- serious - long-term
In obesity, adiponectin levels are _____ and at these levels, it is major predictor of ______ (2)
- very low - hypertension and vascular injury
In terms of SUBCUTANEOUS OBESITY, describe: 1) What there is NOT and what does this imply 2) What type of adipose tissue is seen
1) Ectopic fat deposits in other parts of the body so there is normal metabolic profile 2) "Healthy" adipose tissue
In terms of ENVIRONMENTAL FACTORS related to why we are so obese, describe it in terms of: 1) Food 2) Lifestyle 3) Diversity
1) Surrounded by high fat, energy-dense food 2) Sedentary lifestyle 3) There is diversity in FAT DISTRIBUTION among people in same racial/ethnic background and even with family living in same environment
Once the weight is gained, it is _____
much harder to lose it
Where is ADIPOSE TISSUE mainly found (2)?
- Subcutaneous - Visceral deposits
Adiponectin and leptin both _____ but _____
- reduce weight loss via additive effect - work on different receptors
Where is VISCERAL FAT? What does it have close association with (2)? How much fat is stored here? Where is the rest?
- Abdominal cavity - Close relation with LIVER and DIGESTIVE TRACT - 10 - 20% - Rest (80 to 90%) is in the SUBCUTANEOUS TISSUE
Which fat cells have higher health risks and why?
- Abdominal fat cells - They release contents directly in hepatic portal vein and directly into liver which can cause insulin resistance and increased synthesis of triacylglycerides (TAGs) which can lead to fatty liver BUT lower body fat cells do not act preferentially on hepatic metabolism
What is the dominant underlying risk factors for metabolic syndrome (2)? What is caveat of this? What patients is this true in?
- Abdominal obesity and insulin resistance - Abdominal obesity is NOT an absolute requirement for diagnosis - Those who have insulin resistance and other factors (i.e elevated BP, elevated fasting glucose or decreased high-density lipoproteins) like family history of Diabetes or Asian patients (more insulin resistance)
What is the MAIN CELLULAR COMPONENT of ADIPOSE TISSUE? What is it crucial for (2)?
- Adipocytes - Energy storage and endocrine activity
What is the main cell in ADIPOSE TISSUE? What are other cells present (4)? What do these other cells make up?
- Adipocytes - Precursor cells (pre-adipocytes), Fibroblasts, Immune Cells, Vascular Cells - Stromal Vascular Fraction of the adipose tissue
In terms of WEIGHT GAIN, at first, what happens to ADIPOCYTES? What eventually happens?
- Adipocytes at first (with modest weight gain) EXPAND about 2-3x their normal volume - With LARGE WEIGHT GAIN, the adipocytes reach expansion limitation and eventually PRE-ADIPOCYTES proliferate and differentiate into MATURE FAT CELLS (adipocytes increase in number)
What works similarly to Leptin? What do these do overall? What secretes them? What do they signal?
- Adipolectin - DECREASE appetite - Adipocytes - Signal of fat storage level to brain
What are fat storage level signals to the brain related to appetite and satiety? What do they do overall?
- Adipolectin and Leptin - They DECREASE appetite
What factors seem to play role in obesity (2)? What does this overall cause?
- Genetic predisposition AND environmental/social factors - Causes DISRUPTION in energy balance
What is the MOST RELIABLE measurement of obesity? What is it NOT? How is it calculated?
- Body Mass Index (BMI) - It is NOT a direct measurement of fat - Weight (Kg)/height (m^2)
What is the BODY WEIGHT SET POINT THEORY? What does it require?
- Body weight is regulated at a predetermined or preferred level and it will return to this initial starting point via hormonal mechanisms over the long time period (i.e eat more and lower metabolic energy expenditure if lose weight or decrease appetite and increase energy expenditure if gain weight) - Environmental factors affecting energy use and feeding remain constant
What are the two histological classifications of adipose tissue?
- Brown Adipose Tissue - White Adipose Tissue
What are three prescription medications NOT FDA APPROVED being explored for weight loss? List name and what originally used for
- Bupropion/Wellbutrin (for depression) - Metformin (for diabetes) - Toprimate and zonisamide (for seizures)
What does adiponectin protect against in general? How in general (2)?
- Cardiovascular disease - It is ANTIINFLAMMATORY and ANTIATHEROGENIC
What are four hormones that regulate appetite and satiety?
- Cholecystokinin (CCK) - Leptin - Adiponectin - Ghrelin
What specific hormones (and list where they come from) will DECREASE APPETITE and which ones (and list where they come from) INCREASE DIGESTION?
- DECREASE APPETITE is Leptin and Adipolectin (which are both from adipose tissue) - INCREASE DIGESTION is Cholecystokinin (which is from small intestine)
What happens to fat cells with weight loss following obesity (2)? What does this imply overall (2)?
- Decrease in SIZE - Do NOT decrease in number Difficult to maintain weight loss following obesity because in order to get back to normal weight, need to get fat cells to even SMALLER than normal (since the number cannot be diminished) AND small fat cells are very good at reaccumulating fat which can drive apetite and weight gain
What does METABOLIC SYNDROME cause a significant risk increase in (2)?
- Diabetes - Atherosclerotic cardiovascular disease
What are five different things involved in obesity management that must be integrated and considered?
- Dietary management - Lifestyle modification - Physical activity - Drug therapy - Surgery
What was the original role of adipose tissue thought to be? What is a new role it is discovered to have and how?
- Energy storage organ - Now known to be ENDOCRINE ORGAN that produces hormones called ADIPOKINES
If an individual has a GENETIC PREDISPOSITION to obesity, what else, if anything, is necessary to cause them to be obese often? What is overall happening if obesity is seen?
- Environmental and social influences - Disruption in energy balance
What should moderately overweight people focus on? Instead of what?
- Excercise - Weight reduction
In terms of WEIGHT LOSS after OBESITY, describe what happens to fat cells and whether it is hard to maintain or not and why (2)?
- Fat cells decrease in size BUT not number - Hard since: ---> The fat cells must come down to SMALLER THAN NORMAL SIZE (since can't decrease number of fat cells) to reach normal weight ----> The small fat cells are very good at reaccumulating fat causing increased apetite and subsequent weight gain
Where does the EXTRACELLULAR MATRIX for adipose tissue arise from? What does it function to provide? What can excess matrix cause?
- Fibroblasts - Mechanical support - Adipose tissue dysfunction
What genetic loss caused OBESITY in mice? What is implication of this?
- Genetic loss of LEPTIN - May be able to help treat obesity with LEPTIN
What happens for mortality risks in men and women (and state any difference) with increasing body mass index? What does increasing body mass index often indicate?
- INCREASED mortality for both men and women - Usually means OBESITY possible (especially if > or equal to 30 kg/m^2)
What HEALTH RISKS does obesity have (3)?
- Increased disability - Increased disease - Increase mortality
What are three characteristics of obese adipose tissue?
- Increased number, size and necrotic adipocytes - Immune cell infiltration - Increased pro-inflammatory signals via adipokines
What is EXCESSIVE LIVER FAT a key part of for obesity development (2)? What individuals are most affected by this?
- Insulin resistance and cholesterol abnormalities (so diabetes and cardiovascular disease) - Apple shaped/android/upper body fat
What are the three classifications of ADIPOSE TISSUE?
- Lean adipose tissue with normal metabolic function - Obese adipose tissue with mild metabolic dysfunction - Obese adipose tissue with full metabolic dysfunction
Describe how modest and large weight gain affects fat cells?
- MODEST WEIGHT GAIN causes adipocytes/fat cells to expand (increase size by 2-3x) - LARGE WEIGHT GAIN causes adipocytes to increase in number (pre-adipocytes proliferate and differentiate into adipocytes)
What are the specific immune cells in the adipose tissue usually? What is their major role?
- Macrophages and T-cells - Determine immune status of the adipose tissue
In whom is brown fat very important and why?
- Newborns - Brown fat serves to generate and distribute heat to maintain core body temperature
Where is normal anatomical distribution of adipose tissue? What happens during obesity? What happens as prevalence of obesity increases?
- Normally in SUBCUTANEOUS and VISCERAL deposits - During obesity, adipose tissue EXPANDS in these areas and other areas of body (i.e heart, kidneys, adventitia of blood vessels, liver and abdomen) - Relationship between VISCERAL ABDOMINAL FAT and INSULIN RESISTANCE emerges
What are three other conditions asssocaited with METABOLIC SYNDROME?
- Physical inactivity - Aging - Hormonal imbalance
What two purposes do BLOOD VESSELS in adipose tissue serve?
- Provide nutrients and oxygen especially to adipocytes - Provide conduit for distribution of hormones secreted by adipocytes
A cytokine that is elevated in obesity has receptors in brain, muscle and liver. It has pro-inflammatory effects as well. What is it and its main action?
- Resistin - Increase insulin resistance
What is a cytokine that is elevated during obesity that causes insulin resistance? What else does it do? Where are the receptors for this?
- Resistin - Pro-inflammatory - Brain, muscle, liver
What are the two types of obesity and differentiate them based on the adipose tissue
- SUBCUTANEOUS OBESITY is "healthy" adipose tissue - VISCERAL OBESITY is dysfunctional adipose tissue
What is another name for METABOLIC SYNDROME (2)? What does it cause an increased risk in (2)?
- Syndrome X or Insulin Resistance Syndrome - Diabetes Mellitus and Atherosclerotic Cardiovascular Disease
What are adiponectin levels in obesity? What does this imply?
- Very low - Major predictor of HYPERTENSION and VASCULAR INJURY
Describe difference in two adipose tissues histologically in terms of LIPID DROPLETS?
- White Adipose Tissue has SINGLE lipid droplet while Brown Adipose Tissue has MULTILOCULAR lipid droplets
Leptin is released by _____ in proportion to _____ to work on _____ to _____
- adipocytes - adipose mass - hypothalamus - decrease appetite
As obesity develops, _____ develop hypertrophy due to _____
- adipocytes - increased fatty acid storage
The CNS receives ______ about food intake and energy stores from the ______ (3) and this information is ______ to allow appropriate _____ and ______ to control ______ (2)
- afferent signals - pancreas, gut and adipose tissue - integrated - cognitive - metabolic responses - food intake and metabolism
Excess liver fat plays greater role in obesity for ______ individuals than _____
- apple shaped (android shaped, upper body fat) - pear shaped (gynoid shaped, lower body fat)
Afferent gut signals communicate to the _____ and are regulated by _____
- brain - food intake
Obesity results from a _____ imbalance in ______
- centrally regulated - energy intake vs expenditure
Vascular cells are both ____ and _____
- endothelial cells - vascular smooth muslce cells (associated with major blood vessels)
Adipose tissue is a _____ and _____ organ
- energy storage - endocrine
Body weight is stable if ______ and _____ which is basis for _____
- environmental factors affecting energy use - feeding remain constant - Body Weight Set Point Theory
Management of obesity needs to be ____ and ____ different ______ to _____
- flexible - integrate - therapeutic approaches - meet patient's individual needs
For success in weight loss for obesity, the emphasis should be place on ______ (3)
- healthy lifestyle - diet - preventing weight gain in first place
We must always figure out how to help people maintain a _______ in an environment/society that is conducive to ______
- healthy lifestyle - weight gain
How does weight loss in obese patients result in benefits related to: - blood pressure - TAGs - glucose - lipoproteins - death and what particularly
- lower - lower - lower blood glucose - high HDLs - lower mortality and particular cancer
The immune status of adipose tissue is mainly done via _____ and ____
- macrophages - T-cells
Apetite regulation is mainly controlled by ______ and ______ that interact with _____ (aka ______)
- peripheral hormones - neural signals - CNS - CNS apetite circuit
Obesity is a ____ condition where the individual has a Body Mass Index of _____
- physical - > or = to 30kg/m^2
Success for weight loss in obesity increases with ______ and ______
- psychological/behavioral counseling - long-term support
While _____ is a good diagnostic tool for metabolic syndrome, it is _____ because _____
- waist circumference - not absolutely necessary for diagnosis - just need 3 of the following (elevated blood pressure over 130/85, elevated fasting glucose over 100mg/dL, decreased high density lipoproteins/good cholesterol lower than 40mg/dL for men and 50mg/dL for women, elevated triglycerides over 150mg/dL or increased waist circumference)
Obesity treatment often involves ____ which can happen via ____ and ____ often
- weight reduction - excercise - calorie restriction
In terms of ANATOMIC DIFFERENCES IN FAT DEPOSITION, describe: 1) What body fat position (general, science name and common name) is higher risk than another body fat position (general, science name and common name) 2) Percentage for fat deposits in normal individual (2)
1) - Upper body fat, android shaped, apple shape is MORE RISK than lower body fat, gynoid shape, pear shaped 2) - 80 to 90% in SUBCUTANEOUS deposits - 10 to 20% in VISCERAL deposits
In terms of BIOCHEMICAL DIFFERENCES in REGIONAL FAT DEPOSITS, describe: 1) What are the two main fat cells 2) Differences in two types of cells in terms of - size - turnover - responsive to hormones - release of contents
1) Abdominal fat cells and lower body fat cells 2) - Abdominal fat cells BIGGER - Abdominal fat cells HIGHER RATE of fat turnover - Abdominal fat cells MORE RESPONSIVE to hormones - Abdominal fat cells release contents into HEPATIC PORTAL VEIN and directly into the LIVER which may lead to insulin resistance, increased synthesis of triacylglycerides (TAGs) and more fatty livers while Lower body fat cells do NOT preferentially act on hepatic metabolism and therefore have fewer health risks
In terms of LEPTIN, describe: 1) What makes it 2) What it signals 3) Action
1) Adipocytes 2) FAT STORAGE LEVEL to the brain 3) DECREASES appetite
In terms of ADIPONECTIN, describe: 1) What it is abundant in? 2) What causes it to decrease in general? 3) What secretes it? 4) What it acts like and what does it overall cause? 5) Type of interaction with LEPTIN (something similar and something different) 6) What it is associated in terms of diabetics (2) and what sensitizing is it 7) Two other effects
1) Adipocytes 2) Obesity 3) Adipocytes 4) Acts like LEPTIN and causes WEIGHT LOSS 5) - Both have ADDITIVE EFFECTS - Leptin and Adiponectin work on DIFFERENT receptors 6) Reduced fatty acid circulating and better glycemic control - Insulin sensitizing 7) Anti-inflammatory and anti-atherogenic
In terms of Cholecystokinin (CCK), describe: 1) What it regulates overall 2) What it acts on (generally) and what it does (generally) 3) What happens after CCK acts on what it does in number 2 4) What secretes it 5) What type of signal is it 6) Specific action
1) Appetite and satiety 2) Acts on GI RECEPTORS to SUPPRESS FOOD INTAKE 3) Signals transmitted via VAGUS NERVE to HIGHER BRAIN CENTERS (including amygdala) 4) Small intestine 5) Satiety signal 6) INCREASES digestion
In terms of WEIGHT REDUCTION as treatment for OBESITY, describe: 1) What is often used (2) 2) What does 1 create (2) 3) What is difficult 4) What amount reduction is beneficial and for what specifically (3) often
1) Calorie restriction and excercise 2) - Energy deficit with subsequent weight loss - Cardiorespiratory fitness independent of weight 3) Long-term weight loss maintenance 4) 10% - Lipids, blood pressure, diabetes
In terms of VISCERAL OBESITY, describe: 1) What is seen with energy? 2) What is seen with fatty acids and what does this lead to? 3) What type of adipose tissue is seen and what is this associated with (2) 4) What it correlates with
1) Chronic energy surplus 2) Fatty acid metabolism alteration leading to EXCESS lipid deposits in muscles (including around heart and liver) 3) Dysfunctional/Hypertrophic - Altered metabolic profile - Inflammation 4) Clinical criteria of METABOLIC SYNDROME
In terms of RESISTIN, describe: 1) What it is 2) When is it elevated 3) Where are the receptors (3) 4) What it causes 5) What other effect it has
1) Cytokine 2) Obesity 3) Brain, muscle, liver 4) INSULIN RESISTANCE 5) Pro-inflammatory
As individuals age, describe what happens to: 1) Body Surface Area to Volume ratio 2) Energy expenditure 3) What 1 and 2 is consistent with overall in terms of adipose tissue
1) DECREASES 2) Decreases 3) Levels of BROWN ADIPOSE TISSUE is highest in newborns and decreases with age
In terms of NUMBER OF FAT CELLS IMPORTANCE, describe: 1) What does modest weight gain do to this 2) What does large weight gain do to this 3) Current evidence about fat cells diminishing
1) Does NOT increase the number of fat cells 2) Causes INCREASE in number of fat cells 3) They DO NOT diminish
In terms of BARIATRIC SURGERY, describe: 1) Effectivity (3) 2) Main concern 3) Complications including - intestine and abdominal cavity - legs or lungs - incision site - bowel - syndrome - permanent - gallbladder and kidenys
1) Effective in WEIGHT LOSS, DYSLIPIDEMIA and TRIGLYCERIDE LEVELS in insulin resistance patients 2) It is major surgery and 1 in 200 patients die 3) - Leakage of intestinal contents into abdominal cavity causing infection - Blood clots in legs or lungs - Hernia at incision site - Bowel obstruction - Dumping Syndrome (eating foods high in fat or sugar causing sweating, nausea, vomiting) - Permanent changes in way body absorbs food possibly causing nutrition deficiencies (i.e B12 and anemia) - Gallstones and kidney stones (due to change in absorption of phosphorus, calcium and oxalates)
In terms of DYSLIPIDEMIA, describe: 1) What it is in general 2) What it can be (2)? What is it mostly in developed countries and why (2)? 3) What resistance is seen and what does this cause? 4) What type of adipose tissue is seen and what does it do? 5) What happens to fatty acids (2) 6) What happens to excess of what is produced in 5 7) What happens OVERALL in terms of rise (2) and drop
1) High amounts of lipids in the blood 2) Increased CHOLESTEROL or increased FATTY ACIDS - HYPERlipidemia so elevations of lipids due to diet and lifestyle 3) Insulin resistance and this causes increased insulin production 4) Insulin resistant adipose tissue AND it produces more hormone sensitive lipase (HSL) 5) Circulating levels rise and they are converted to triaclyglcerols (TAGs) and cholesterol in the liver 6) Excess TAGs and cholesterol are relased as VLDL (very low density lipoproteins) which have large amounts of TAGs and bad cholesterol that can build on arterial walls 7) - Serum TAGs and CHOLESTEROL rise - HIGH DENSITY LIPOPROTEIN (HDL) drops
In terms of OBESE ADIPOSE TISSUE, describe its characterization in terms of 1) Adipocytes (3) 2) Other cells 3) Signals and how
1) Increased SIZE and NUMBER (if large weight gain for latter) and NECROTIC 2) Infiltration of immune cells 3) Increased pro-inflammatory signals via ADIPOKINES
What are secondary effects of obesity in terms of: 1) Fatty acids and why 2) Adiponectin levels 3) Insulin resistance factors and give example 4) Certain mediators and example 5) Peripheral tissues (2) and what does this mediate and what does this cause to a certain organ
1) Increased circulating due to net increase in lipolysis 2) Reduced 3) Increased like RESISTIN 4) INCREASE in PRO-INFLAMMATORY MEDIATORS like TNF-ALPHA 5) Accumulation of TRIGLYCERIDES and LONG CHAIN FATTY ACIDS - Mediates INSULIN RESISTANCE - Impairs PANCREATIC BETA CELLS (due to lipotoxicity and impaired function in general)
In terms of ORLISTAT, describe: 1) What it is and what it does 2) Effect on weight 3) What it must be used with 4) How it affects other important things 5) Side effects (2) and rare report
1) Lipase inhibitor that decreases breakdown of dietary fat 2) MODEST weight loss (5-10lbs over 6 months) 3) Reduced calorie and LOW FAT diet 4) DECREASES absorption of fat soluble vitamins A, D, E and K 5) - Loose and oily stool - Liver disease (rare)
In terms of OBESITY and ADIPONECTIN, describe: 1) What levels are adiponectin generally in obesity? 2) What does 1 imply then (2) 3) What does adiponectin specifically do related to 2 4) What adiponectin overall protects against?
1) Low 2) Adiponectin is a major predictor of HYPERTENSION and VASCULAR INJURY 3) - ADIPONECTIN regulates expression of many factors that control endothelial cell health so it helps protect against endothelial dysfunction - ADIPONECTIN regulates several factors that promote plaque initiation and progression that are seen in cardiovascular disease 4) Cardiovascular disease
In terms of BROWN ADIPOSE TISSUE, describe: 1) Who has highest levels in terms of age and what happens as time progresses 2) Do lean or obese people have higher levels? 3) What new research suggests in terms of brown adipose tissue levels and relation to white adipose tissue 4) Obesity relation in terms of research 5) Where adult brown adipose tissue deposits (3)
1) Newborns - As people age, they have LESS brown adipose tissue 2) Lean 3) Can INCREASE brown adipose tissue - Can convert WHITE ADIPOSE TISSUE to BROWN ADIPOSE TISSUE 4) May be potential treatment for obesity based on fact that obese mice with lean mice brown adipose tissue had decreased weight and decreased insulin resistance 5) - Cervical/supraclavical - Perirenal/adrenal - Paravetebral (around major blood vessels)
In terms of LEPTIN, describe: 1) What it communicates and to what 2) What it is released in proportion to? What does it act on? What does it do? 3) What it causes when it is released on weight 4) What scenario is this decreased in? Why? 5) How obesity is specifically related to this? What helps clinically support this?
1) Nutritional status to your body and brain 2) - Released in proportion to ADIPOSE MASS - Acts on HYPOTHALAMUS - Works to DECREASE APPETITE 3) Weight loss 4) Starvation since want HUNGER for starvation reversal (which is counteracted with leptin) 5) Obesity in humans seems to be due to defects in LEPTIN SIGNALING and not decrease in synthesis, release or receptors - Leptin injections ONLY WORK in leptin-deficient individuals
In terms of SIBUTRAMINE, describe: 1) Current use and why 2) Mechanism
1) Recalled because increased risk of heart attack AND stroke 2) Reduces re-uptake of serotonin and norepinephrine so it is appetite suppressant
In terms of BROWN ADIPOSE TISSUE (BAT), describe: 1) How it differs from White Adipose Tissue mainly and generally (2) 2) Shape and droplets 3) Color 4) Function and who it is really important for?
1) SHAPE and NUMBER OF DROPLETS 2) - Polygonal shape - Mutilocular lipid droplets (white adipose tissue only has one lipid droplet) 3) Increased number large spherical mitochondria 4) Generate and distribute heat to maintain core body temperature - Newborns
In terms of WIEGHT LOSS after OBESITY, describe: 1) What is the problem? 2) What was a study and results of that study done for this? 3) What was a rationale for the results seen in 2
1) SHORT TERM WEIGHT LOSS is readily achieved through dietary restriction but only a small minority of obese people MAINTAIN WEIGHT LOSS LONG TERM 2) - 50 overweight/obese patients were put on strict diet for 8 weeks to lose 10% body weight (about 30 lbs) and then gradually (study) - RESULTS indicated that despite counseling and written advice on how to maintain new weights, they gained about 12 lbs after a year and were hungrier after meals after dieting (compared to before dieting) 3) Hormone levels that ENCOURAGE WEIGHT REGAIN and INCREASED APPETITE do NOT return to levels recorded before weight loss (CCK and Leptin, which are satiety signals, remain low AND Grhelin, which increases appetite, remains high)
In terms of GHRELIN, describe: 1) What secretes it 2) What it does
1) Stomach 2) Increases appetite
In terms of GENETIC FACTORS for why we are obese, describe it in relation to: 1) A theory 2) Twins and adopted children 3) Certain drive and why (2) 4) Dietary fats (2) 5) General
1) THRIFTY GENE THEORY - We have genetic tendency to accumulate fat left over from days when there was high energy activity and scarce food 2) - Identical twins raised apart showed similar weight gain (distribution, amount and Body Mass Index) as biological parents - Adopted children showed similar BMI to biological parents 3) Drive to overeat due to poor regulation of appetite and satiety 4) - Diminished ability to use fatty acids as fuel - Enlarged, easily stimulated capacity to store body fat 5) Some genes (over 360) found to be associated with obesity
What is the average turnover time for adipocyte?
10 years
In terms of the CRITERIA for DIAGNOSIS of METABOLIC SYNDROME, describe what it is (5 possibilities)
ABNORMAL LEVEL OF ATLEAST 3 OF THESE CRITERIA - Elevated waist circumference (abdominal obesity) - Elevated triglycerides - Reduced high-density lipoprotein cholesterol (HDL or good cholesterol) - Elevated blood pressure - Elevated fasting glucose
What is OBESITY? What is the essential problem?
Abnormal accumulation of body fat as a result of chronic energy imbalance - Calories consumed > calories expended
What is require for adipose tissue to get proper flow of nutrients and oxygen?
Blood vessels
What is more accurate measurement of obesity, body mass index or increased waist size?
Body Mass Index (BMI)
What promotes FULL METABOLIC DYSFUNCTION in obesity?
Chronic, low grade inflammatory state
What is QSYMIA?
Combination of PHENTERMINE (appetite suppressant) and TOPIRAMATE (epilipesy)
Describe a genetic reason why we may be obese related to dietary fats?
Diminished ability to use dietary fats as fuel but enlarged, easily stimulated capacity to store body fat
What is LORCASERIN HYDROCHLORIDE?
FDA approved appetite suppressant
True/False: Leptin injections help all obese patients
False (Leptin only helps leptin-deficient patients since it seems obesity related to leptin is through signaling and not release, receptors or amount)
True/False: Modest weight gain increases the number of fat cells
False (expands the VOLUME 2-3x often)
True/False: Bariatric surgery should be used in everyone for treatment
False (need to consider that it is a major surgery and 1 in 200 people die)
True/False: Adipocytes can remodel in adipose tissue and turnover at fast rate
False (they can remodel but do NOT turnover at fast rate...it is 10 years lifespan for adipocyte)
What is up to 50% of the variability of body weight in individual governed by?
Genetic factors
What is secreted from the stomach and increases appetite?
Ghrelin
What can the increasing prevalence of metabolic syndrome in the US be explained by?
Growing epidemic of OBESITY
What do identical twins raised apart show in terms of weight gain (define three parameters)? What about adopted children in terms of BMIs?
IDENTICAL TWINS - Show similar weight gain (distribution, amount and Body Mass Index) as biological parents ADOPTED CHILDREN - Show similar BMIs to biological parents
What does obesity do to fat cells and list caveat (2)?
Increase NUMBER and SIZE of fat cells but only increase NUMBER if LARGE WEIGHT GAIN but if MODEST WEIGHT GAIN then only increase SIZE
What makes Brown Adipose Tissue its color?
Increased number of large spherical mitochondria
What has obesity incidence increase brought upon in terms of another disease?
Increased obesity has lead to NON-ALCOHOLIC FATTY LIVER DISEASE increasing as well
How does ADIPOSE TISSUE do its ENDOCRINE ROLE?
Release of hormones called ADIPOKINES
Where does adipose tissue get stored in obesity besides normal locations which are ____ and ___? (5)
NORMAL - Visceral deposits - Subcutaneous deposits OBESITY - Heart - Kidneys - Adventitia of blood vessels - Liver - Abdomen
Describe correlation of OBESITY and INCREASED WAIST SIZE?
Obesity IS correlated with increased waist size but it is NOT accurate measurement as is BMI (Body Mass Index)
What seems to promote obesity linked metabolic disorders?
Pro-inflammatory signals
What relationship is seen with prevalence of obesity increasing?
Relationship between VISCERAL ABDOMINAL FAT and INSULIN RESISTANCE
What type of obesity is "HEALTHY" adipose tissue?
Subcutaneous obesity
Is more fat normally deposited in SUBCUTANEOUS TISSUE or VISCERAL TISSUE?
Subcutaneous tissue (80 to 90% here compared to 10 to 20% in visceral)
What is general relationship between fat, leptin and effect
The MORE FAT you have means MORE LEPTIN and LESS APPETITE (less food you eat)
What is the STROMAL VASCULAR FRACTION of adipose tissue?
The four cell types besides adipocytes and these are vascular cells, fibroblasts, precursor/pre-adipocytes and immune cells
What are the levels generally of brown adipose tissue in LEAN PEOPLE?
They are HIGH
What has been seen to link BROWN FAT and OBESITY?
Transplanting brown fat from LEAN MICE to OBESE MICE induces weight loss and improves insulin resistance in the obese mice
True/False: Body mass index criteria are different for adolescents and children
True
True/False: We do not know how to successfully "treat" obesity
True
True/False: Over 300 genes have been found to be associated with obesity
True (though some may have small roles)
What obesity correlates with METABOLIC SYNDROME?
Visceral obesity
What type of obesity is DYSFUNCTIONAL adipose tissue?
Visceral obesity
Metabolic syndrome is associated with _____ and includes: - something related to glucose - something related to insulin (2) - something related to lipids - something related to blood pressure - something related to risk (2)
abdominal obesity - glucose intolerance - insulin resistance, hyperinsulinemia - dyslipidemia - hypertension - significant risk factor for diabetes and atherosclerotic cardiovascular disease
Obesity is linked to _____ that promotes metabolic dysfunction
chronic, low grade inflammatory state
Obesity is essentially caused by _____
disruption in energy balance
