Obesity Lecture and Workshop Flashcards

1
Q

Does environment play a huge role in heritability of obesity?

A

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.

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2
Q

What did the obesity genome wide association study find?

A

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.

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3
Q

What is the hostile environment?

A

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.

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4
Q

What is the thrifty gene set point theory?

A

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.

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5
Q

What is the thought cause of obesity?

A

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

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6
Q

What happens if you eat 100kcal a day more than you expend for a year?

A

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

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7
Q

How does increased adiposity lead to atherosclerosis and CVD?

A
  • 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.
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8
Q

What other conditions are also associated with increased adipose tissue?

A

diabetes and sleep apnea

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9
Q

What do lower levels of Vit D cause?

A

increased obesity

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10
Q

What is intrathoracic and pericardial fat found to be associated with?

A
  • higher BMI, waist circumference and visceral abdominal fat.
  • increased TG, Hypertension, diabetes
  • decreased HDL
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11
Q

What does pericardial fat lead to?

A

coronary artery calcification and atherosclerosis

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12
Q

What does intrathoracic fat lead to?

A

abdominal aortic calcification and atherosclerosis of the aorta

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13
Q

What is the global affect of visceral fat?

A

leads to negative effects on the whole body and can have potential for local toxic effects on the vasculature

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14
Q

what are short-acting satiation signals?

A
  • short act rapidly to influence food intake

- promotes meal termination

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15
Q

Where do short-acting signals come from and where do they act?

A
  • originate from stomach, proximal and distal small intestine, pancreas.
  • act on the hindbrain (input received here)
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16
Q

what are long-acting satiation signals?

A

long-acting act more slowly to maintain fat stores. They include all the orexigenic and anorexigenic peptides.

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17
Q

Where do long-acting signals act?

A

act on the brainstem, arcuate nucleus, paraventricular nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, lateral hypothalamic area and then all converge at the hypothalamus.

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18
Q

What are the two types of central and peripheral hypothalamic peptides?

A

orexigenic (promote weight gain) and anorexigenic (promote weight loss)

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19
Q

What are 2 central orexigenic peptides?

A
Neuropeptide Y (NYP) 
Agouti-related peptide (AGRP)
20
Q

What is one type of central anorexigenic peptide?

A

melanocortins

21
Q

What is a peripheral orexigenic peptide?

A

Ghrelin

22
Q

What are 4 peripheral anorexigenic peptides?

A
  1. Leptin
  2. Peptide YY
  3. Cholecystokinin (CCK)
  4. Insulin
    * *CLIP**
23
Q

What is NPY?

A
  • 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
24
Q

What increases NPY synthesis and secretion?

A
  • increased food and energy deprivation

- decreased leptin and insulin

25
Q

Where is AGRP produced?

A

ARC, is co-secreted with NPY and projects to the hypothalamus (PVN and DMH)

26
Q

What does AGRP do?

A
  • increases melanocortin receptors (increased hunger)

- leads to hyperphagia and obesity

27
Q

What inhibits AGRP release?

A

Leptin

28
Q

Where is Ghrelin made?

A

endocrine cells of gastric muscosa, also in the proximal SI, pituitary, hypothalamus, pancreas, lung, plancenta, ovary, testis, kidney, tumors.

29
Q

What does Ghrelin do?

A
  • 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?
30
Q

Melanocortins are produced where and what is the function?

A
  • come from POMC in hypothalamus (POMC stimulated by leptin)
  • inhibits feeding (anorectic peptide)
  • inhibits AGRP
31
Q

What happens if there is a mutation in the MC4 receptor?

A

OBESITY! MSH has to bind to MC4 to inhibit feeding. If no inhibition, then keep eating

32
Q

Where is Peptide YY made and what does it do?

A
  • intestinal L cells, found in high concentrations in distal GI tract
  • released following food intake
  • delays gastric emptying, secretions from the stomach and pancreas
  • increases absorption of fluids and electrolytes from the ileum.
  • causes weight loss
  • ## acts on ARC receptors inhibiting NPY/AGRP neurons and stimulating POMC
33
Q

What are peptide YY levels in obese people?

A

lower levels leading to increased eating and obesity

34
Q

Where is CCK made and what does it do?

A
  • GI tract and brain
  • released in response to nutrients/fats/proteins
  • decreases meal size, may interact with leptin to decrease food intake
35
Q

If you have a lot of adipose tissue, how much leptin do you have?

A

lots of leptin. Directly related

36
Q

Where is leptin made and what does it do?

A
  • white adipose tissue

- causes decrease in weight (if there is a problem with the OB gene, then less leptin and you get fat)

37
Q

How does leptin decrease food intake?

A
  1. binds to Ob-Rb receptor in the ARC, PVN, DMH and LHA
  2. stimulates cascade inhibiting NPY, MCH, AGRP (orexigenic peptides)
  3. stimulates MSH, CRF (anorectic peptides)
38
Q

What do increased and decreased levels of leptin tell the brain?

A

increased– lots of adipose being stored and decreases appetite
decreased– when loosing weight due to food restriction, leptin is suppressed.

39
Q

Why is waist circumference an important assessment of an obese patient?

A

visceral abdominal fat is more metabolically active

40
Q

Where are the “controls” for caloric intake/output and weight control?

A
GI tract (peripherals)
hypothalamus (central)
41
Q

What is orlistat?

A
  • GI lipase inhibitor that leads to 2.9kg weight loss
  • decreased incidence of diabetes and TC, LDL, BP and glycemic control
  • negatives: decreased HDL
  • FDA approved
42
Q

What is sibutramine?

A
  • centrally acting monoamine reuptake inhibitor.
  • 4.2kg weight loss
  • RAISED HDL (good)
  • negative: raised BP and HR
  • No longer FDA approved in the USA
42
Q

What is rimonabant?

A
  • CB1 receptor antagonist
  • taken off the market due to side effects of depression and suicide
  • still on the market in the UK
42
Q

What is Lorcaserin?

A
  • selective serotonin 5HT2C receptor agonist
  • 3.6% wt loss
  • thought to possibly be related to different cancers
  • FDA approved
44
Q

What is Phentermine/topiramate?

A

phentermine: appetite suppressant/amphetamine
topiramate: anti-convulsant
- 9.2% wt loss
- limited side effects, memory, attention
- FDA approved for longterm
- phentermine by itself is only approved for short term

45
Q

What is Phentermine/topiramate?

A

phentermine: appetite suppressant/amphetamine
topiramate: anti-convulsant
- 9.2% wt loss
- limited side effects, memory, attention
- combo is FDA approved for longterm
- phentermine by itself is only approved for short term