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Regulatory Physiology and Pharmacology > Obesity 2 > Flashcards

Obesity 2 Flashcards

1
Q

What is NPY?

A

a 36aa peptide that stimulates food intake and reduces energy expenditure

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2
Q

What do high a-MSH levels do?

A

inhibit food intake

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3
Q

When is POMC gene expression increased?

A

when food intake

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4
Q

What does activation of MC3 and MC4 do?

A

suppresses food intake with agonists

enhances food intake with antagonists

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5
Q

What is the phenotype of the Ay mouse?

A 
yellow
obese
hyperglycemic
insulin resistant
leptin resistant
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6
Q

What does the Ay gene encode?

A

AGOUTI - the natural antagonist of the MC receptors - (1 for hair colour, 4 for obesity)

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7
Q

What is agouti related protein?

A

co-expressed with NPY in ARC neurons and are antagonists to MC3 and MC4
causes long lasting increased food intake

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8
Q

What does the fa gene do?

A

results in leptin insensitivity

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9
Q

What is the mutation in the fa gene?

A

Q269P

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10
Q

What is the fat mutation?

A

mutation in CPE which is responsible for cleavage of POMC and thus a-MSH

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11
Q

What does the fat mutation cause?

A

massive obesity

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12
Q

What is the tubby mutation?

A

produces truncated protein modelling adult onset obesity

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13
Q

What are the obesity genes in humans?

A 
rarely Ob
occassionaly db
Loss of function POMC mutations
No CPE but PC1 
Mutations in MC4
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14
Q

where does Leptin therapy work?

A

only in those who have no leptin

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15
Q

where does Leptin therapy work?

A

only in those who have no leptin

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16
Q

What are the two main theories in leptin resistance?

A

defective transport into the brain

altered signal transduction following binding to receptor

17
Q

What is significant about the PTP-1B knockout mouse?

A

resistant to diet induced obesity and diabetes

18
Q

What is PTP-1B?

A

an enzyme which curtails leptin and insulin signalling

19
Q

What does the IRS-2 KO mouse display?

A

neuronal resistance to leptin and insulin

20
Q

What is SOCS3?

A

a suppressor of cytokine signalling

21
Q

What does SOC3 do?

A

inhibits JAK-STAT signalling, binds to Ob-Rb and prevents leptin signalling

22
Q

What is associated with induction of SOCS3 in the hypothalamus?

A

leptin resistance

23
Q

How does SOCS3 negatively regulate insulin signalling?

A

reduced IRS-mediated signalling

24
Q

What else is considered to be contributors to hypothalamic resistance?

A

SHP2
Hyperleptinemia
ER stress
Inflammation

25
Q

What are some previous drugs for treatment of obesity?

A

Noradrenergics - CV side effects, appetite suppressants

Serotonergics - appetite suppressants on 5-HT system

26
Q

What was the problem with Sibutramine?

A

strokes and cardiovascular side effects

27
Q

How did Orlistat work?

A

inhibited pancreatic lipase by decreased triglyceride absorption
reduces efficiency of fat absorption in sm. intestine

28
Q

What is the problem with orlistat?

A

need supplements, can cause cramping and diarrhoea

29
Q

What is signifcant about CB1 KO mice?

A

have decreased appetite and are lean

30
Q

What is the issue with Rimonabant?

A

caused sever depression and anxiety and increased risk of suicide

31
Q

What is Larcaserin?

A

5HT2c receptor agonist

32
Q

What is Qsymia?

A

combination therapy - topiramate with phentermine - dosage reduced for approval

33
Q

What is Contrave?

A

combination of opioid antagonist and dopamine uptake inhibiter - CV issues

34
Q

What is Contrave?

A

combination of opioid antagonist and dopamine uptake inhibiter - CV issues

35
Q

What is the most effective obesity treatment?

A

Bariatric Surgery

36
Q

Why is Bariatric surgery so effective?

A

high level of resolution of T2DM

may affect peptide secretions

Regulatory Physiology and Pharmacology (14 decks)

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