Flashcards in Obesity Lecture and Workshop Deck (46)
Does environment play a huge role in heritability of obesity?
No. Kids who had no exposure to their biological parents still had a similar weight, suggesting that environment didn't play as important of a role as genetics.
What did the obesity genome wide association study find?
lots of genes are associated with obesity, however they only account for a very small percentage in the variation of BMI (not the only thing that determine obesity.
What is the hostile environment?
aka the feast environment. Lifestyle that increases caloric intake by decreasing the amount of exercise etc that we get. We evolved to be able to effectively store our calories in case of a famine, but now we live in a constant feast environment so we store more calories as fat than we need to.
What is the thrifty gene set point theory?
says that we were created to be able to survive both feast and famine conditions. In times of famine, we needed decreased energy expenditure and increased efficiency to prevent weight loss. Therefore, during times of feast there is maximum energy storage as adipose tissues. So we developed all this different mechanisms to prevent weight loss but not many mechanisms to prevent weight gain. People with this "gene" expend less energy and therefore gain weight.
What is the thought cause of obesity?
Back in the day we were hunger gatherers who lived in distinct feast or famine environments. Those who survived stored energy as adipose and therefore gained weight. Now that we live in a hostile environment "feast-feast" there is more food=more storage=more adipose even though we don't have to worry about famine
What happens if you eat 100kcal a day more than you expend for a year?
you would gain 12 pounds a year. this is the estimated excess that we would have to be consuming to account to the recent trends in weight gain
How does increased adiposity lead to atherosclerosis and CVD?
- leads to inflammation and increased IL-6 and antiotensinogen, decreased adiponectin.
- this disrupts endothelial function and causes insulin resistance which leads to atherosclerosis and CVD.
What other conditions are also associated with increased adipose tissue?
diabetes and sleep apnea
What do lower levels of Vit D cause?
What is intrathoracic and pericardial fat found to be associated with?
- higher BMI, waist circumference and visceral abdominal fat.
- increased TG, Hypertension, diabetes
- decreased HDL
What does pericardial fat lead to?
coronary artery calcification and atherosclerosis
What does intrathoracic fat lead to?
abdominal aortic calcification and atherosclerosis of the aorta
What is the global affect of visceral fat?
leads to negative effects on the whole body and can have potential for local toxic effects on the vasculature
what are short-acting satiation signals?
- short act rapidly to influence food intake
- promotes meal termination
Where do short-acting signals come from and where do they act?
- originate from stomach, proximal and distal small intestine, pancreas.
- act on the hindbrain (input received here)
what are long-acting satiation signals?
long-acting act more slowly to maintain fat stores. They include all the orexigenic and anorexigenic peptides.
Where do long-acting signals act?
act on the brainstem, arcuate nucleus, paraventricular nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, lateral hypothalamic area and then all converge at the hypothalamus.
What are the two types of central and peripheral hypothalamic peptides?
orexigenic (promote weight gain) and anorexigenic (promote weight loss)
What are 2 central orexigenic peptides?
Neuropeptide Y (NYP)
Agouti-related peptide (AGRP)
What is one type of central anorexigenic peptide?
What is a peripheral orexigenic peptide?
What are 4 peripheral anorexigenic peptides?
2. Peptide YY
3. Cholecystokinin (CCK)
What is NPY?
- one of the most abundant peptides in the hypothalamus, central orexigenic
- ARC is the most major site of expression in neurons that project to the PVN.
- chronic administration results in hyperphagia, decreased thermogenesis and obesity
What increases NPY synthesis and secretion?
- increased food and energy deprivation
- decreased leptin and insulin
Where is AGRP produced?
ARC, is co-secreted with NPY and projects to the hypothalamus (PVN and DMH)
What does AGRP do?
- increases melanocortin receptors (increased hunger)
- leads to hyperphagia and obesity
What inhibits AGRP release?
Where is Ghrelin made?
endocrine cells of gastric muscosa, also in the proximal SI, pituitary, hypothalamus, pancreas, lung, plancenta, ovary, testis, kidney, tumors.
What does Ghrelin do?
- signal for meal initiation, levels are high right before a meal.
- stimulates NPY and AGRP in ARC
- antagonizes leptin-induced inhibition of food intake
- obese patients may be less sensitive to ghrelin?