Q: What is the formula for BMI? A: weight(kg)/height (m)^2 Q: What are the BMI values for "overweight"? A: 25-30 kg/m^2 Q: What is the BMI value for clinical obesity? A: >30 kg/m^2 Q: What is the BMI value for morbid obesity? A: >40 kg/m^2 Q: Women with abdominal obesity are less efficient at breaking down what? What can this lead to? A: Glucose; Diabetes Q: How can body weight be directly related to development of congestive heart failure? A: Increased total body oxygen, cardiac output, structural changes of the heart, LV hypertrophy, sys & dias dysfunction Q: What are two (opposite) explanations for the cause of human obesity? A: 1) Fundamental lack of discipline (mmm.. Whopper) 2) Body weight is physiologically controlled (hey, not my fault) Q: What is the "depletion-repletion" model of controlling weight? A: Some parameter of immediately available energy is constantly monitored Q: What is the "lipostatic model" of controlling weight? A: Signals proportional to the size of fat stores become integrated with other regulators of food intake Q: Giving rats CCK before a meal would cause them to do what? A: Eat less Q: What are some of the satiety factors? What would happen if you block these? A: CCK, bombesin, gastrin-releasing peptide, neuromedin B, glucagon; You don't feel full & eat more. Q: Satiety peptides work neuronally in what two ways? A: 1) Act through receptors in the brain itself 2) Act through peripheral nerves (eg Vagus) Q: Do satiety factors alter body wieght? A: NO! They just alter meal size, not body weight. You just eat more meals. Q: What hormones does white adipose tissue secrete? A: leptin, acylation-stimulating protein (ASP), angiotensinogen, adiponectin, resistin, & "steroid" hormones Q: Fat does more than just jiggle; what homeostatic functions does it perform? A: endocrine function, glucose and lipid metabolism, vascular homeostasis, immune response & reproduction Q: What happens to adipose secreted proteins when the adipose tissue is markedly altered? A: The secreted proteins are dysregulated. Q: What 4 things to leptin and insulin have in common when it comes to controlling feeding behaviour? A: 1) Both circulate at levels proportional to body fat, 2) both enter CNS in proportion to plasma level, 3) both RECEPTORS are expressed in brain neurons involved in energy intake, 4) administration directly into brain reduces food intake Q: Is leptin or insulin more important in controlling energy homeostasis (& thus obesity)? A: Leptin Q: Where is the "satiety center" of the brain? A: The ventromedial hypothalamic nucleus (VMN) Q: Where is the "hunger center" of the brain? A: The lateral hypothalamic area (LHA) Q: What does the arcuate nucleus do? A: It transduces info. related to signaling by leptin into a neuronal response (a hypothesis, at least) Q: What does adiponectin do? A: It is released by fat cells and it stimulates fatty acid oxidation, decreases plasma triglycerides, and improves glucose metabolism by increasing insulin sensitivity Q: What problems does hypoadiponectemia cause? A: contributes to insulin resistance & accelerated artherogenesis Q: What does resistin do? A: It is involved in the development of insulin resistance in white adipose tissue of obese rats Q: What does ghrelin do? Where does it act? When it is released? A: It is a regulatory peptide that is made in the gut and acts on the hypothalamus to oppose leptin & stimulates energy gain and secretion of growth hormone; it is released in response to fasting Q: Do patients that have undergone gastic bypass surgery have higher or lower levels of ghrelin compared to people who have lost weight from dieting? A: Lower. This may explain why they can keep the weight off. After "normal" dieting, people have a higher level of ghrelin. Q: What is a long-term regulator of body weight? A: Gastric ghrelin. Q: Gastric ghrelin functions as part of what pathway? A: The orexigenic pathway "centering on NPY and AGRP in the ARC of the hypothalamus." pg. 45 Q: The increased expression of ghrelin mRNA is characteristic of an ob/ob (obese) genotype in mice, resulting in an obese phenotype. What reverses this phenotype? A: Immunoneutralization with anti-ghrelin antiserum. Q: What levels of ghrelin are found in obese people after they lose weight? A: Higher. Q: What levels of ghrelin are found in obese people after they undergo gastric bypass surgery? A: Lower Q: What do lower levels of ghrelin after bypass surgery suggest about its successfulness in helping people lose weight compared to dieting? A: It is more successful. Q: What is the interaction between ghrelin and leptin in regulation of feeding and body ? A: Competitive. Q: Ghrelin stimulates and leptin inhibits what neurons? A: NPY/AGRP neurons. Q: Ghrelin reinforces the idea that the stomach is important for what? A: Regulation of appetite by secreting either satiety-inducing peptides (CCK) or orexigenic peptides (ghrelin). Q: Neurons that promote orexia (food-seeking) secrete what? A: NPY/AgRP, see pg. 45. Q: Neurons that promote anorexia (fasting) secrete what? A: POMC/CART. Q: Injection of what neuropeptide into cerebral ventricles stimulates food intake? A: Neuropeptide Y (NPY). Q: During active depletion of body fat stores, NPY gene expression increases or decreases? A: Increases. Q: What inhibits NPY gene expression in the arcuate nucleus? A: Leptin. Q: What other hormones in addition to NPY have been added to the list of anabolic effector signaling molecules? A: AGRP (Agoutin-related protein), orexin, and melanin-concentrating hormone (MCH). Q: Catabolic effector signaling molecules promote what? A: Negative energy balance. Q: Catabolic effector signaling molecules fall into what major category? A: Melanocortins, see middle of pg. 45 for details. Q: Melanocortins are cleaved from which precursor molecule? A: pro-opiomelanocortin (POMC) precursor molecule. Q: If melanocortins promote negative energy balance, what phenotype would mice and humans lacking the melanocortin 4 (MC4) receptor exhibit? A: Hyperphagic and very obese. Q: How does leptin regulate energy balance? A: By modulating the catabolic and anabolic neuropeptides. Q: Mutations in pro-opiomelanocortin (POMC) precursor molecule lead to what? A: Obesity. Q: Why do a mutation in the melanocyte-stimulating hormone (MSH) receptor (MC4R) cause obesity? A: It leads to a defect in MSH signalling, resulting in leptin resistance. Q: Mutation in the leptin receptor leads to what? A: You guessed it, obesity. Q: Neurons in the caudal brainstem (input from vagus) control appetite by releasing what class of neurotransmitters? A: Monoamine neurotransmitters. Q: Give three (3) examples of monoamine neurotransmitters. A: Noradrenaline, dopamine, and serotonin. Q: Injection of what monoamine neurotransmitter into the PVN (paraventricular neurons) increases food intake? A: Noradrenaline. Q: How might you predict leptin affects noradrenaline release? A: Leptin inhibits noradrenaline release. Q: Depletion of dopamine results in what? A: Feeding deficits. Q: Increasing Serotonin levels may lead to what? A: Weight loss, but serotonin does not seem to have the same robust effect on obesity that lack of MC4 or leptin receptors has. Q: Drugs that increase serotonin-receptor signaling would do what to food intake? A: Suppress food intake. Q: Recent findings suggest that leptin affects serotinin in what way? A: Leptin increases serotonin turnover. Q: What proportion of Americans have a normal body mass index (BMI)? A: Less than 40%. Q: How well are the mechanisms by which environmental factors modulate the physiological system involved in weight control? A: Poorly understood. Q: A high-fat diet leads to resistance to what important hormone? A: Leptin. Q: Anti-obesity drugs are classified according to what? A: Primary mechanism of action on energy balance. Q: What is the goal of all anti-obesity drugs? A: To induce and maintain a state of negative energy balance. Q: What are the four general classes of anti-obesity drugs? A: 1.) Inhibitors of food intake (i.e. appetite suppressants), 2.) Inhibitors of fat absorption, 3.) Enhancers of energy expenditure, 4.) Stimulators of fat mobilization. Q: How do drugs that enhance energy expenditure work? A: They increase thermogenesis WITHOUT requiring increases in physical activity. Q: How do drugs that stimulate th mobilization of fat work? A: They act peripherally to reduce fat mass or decrease triglyceride synthesis or BOTH. Also do not require increased physical activity. Q: The beneficial effects of anit-obesity drugs can be overcome by what two behaviors? A: 1.) increased food intake, and 2.) decreased physical activity. Q: Only a few anti-obesity drugs have been approved, how do these drugs work? A: Appetite suppressants which modulate the levels of monoamine neurotransmitters (specifically serotonin and norepinephrine) in the brain. Q: In response to therapeutic leptin administration, weight loss appears to be entirely due to what? A: Loss of fat. Q: Therapeutic leptin administration promised to be an important approach to fighting obesity, what did a recent clinical trial show about its effectiveness? A: Very modest, if any, benefit. Only the two highest leptin doses showed significant results. Q: What is surprising about the leptin concentrations in obese mammals? A: They have elevated leptin plasma concentrations and seem to be resistant to leptin-induced anorexia. Q: What diseases correlate strongly with obesity, and will affect more children as incidence of juvenile onset obesity continues to rise? A: non-insulin-dependent diabetes mellitus, hypertension, coronary artery disease, and other cardiac disorders. Q: Excessive deposition of triacylglycerol (TG) in nonadipose tissues (steatosis) enlarges WHAT POOL of fatty acyl-CoA? And what negative effect does this have? A: Increases in INTRACELLULAR pools of fatty acyl-CoA provides more substrate for non-oxidative metabolic pathways, which leads to ceramide synthesis. Q: Increases ceramide synthesis leads to what? A: Cell dysfunction and death through apoptosis. Q: What capacity do nonadipocytes have for storing excess fat? A: Limited capacity. Q: When exposed to high levels of plasma lipids, nonadipocytes undergo what process? A: Steatosis, loss of function, and eventually, FA-induced "lipoapoptosis." Q: What might be the causal link between steatosis and cardiac function? A: Increased TGs leads to increased fatty acyl-CoA, which provides increased substrate for ceramide (pro-apoptosis) synthesis.