Obesity 2 Flashcards Preview

Regulatory Physiology and Pharmacology > Obesity 2 > Flashcards

Flashcards in Obesity 2 Deck (36):
1

What is NPY?

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

2

What do high a-MSH levels do?

inhibit food intake

3

When is POMC gene expression increased?

when food intake

4

What does activation of MC3 and MC4 do?

suppresses food intake with agonists
enhances food intake with antagonists

5

What is the phenotype of the Ay mouse?

yellow
obese
hyperglycemic
insulin resistant
leptin resistant

6

What does the Ay gene encode?

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

7

What is agouti related protein?

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

8

What does the fa gene do?

results in leptin insensitivity

9

What is the mutation in the fa gene?

Q269P

10

What is the fat mutation?

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

11

What does the fat mutation cause?

massive obesity

12

What is the tubby mutation?

produces truncated protein modelling adult onset obesity

13

What are the obesity genes in humans?

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

14

where does Leptin therapy work?

only in those who have no leptin

15

where does Leptin therapy work?

only in those who have no leptin

16

What are the two main theories in leptin resistance?

defective transport into the brain
altered signal transduction following binding to receptor

17

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

resistant to diet induced obesity and diabetes

18

What is PTP-1B?

an enzyme which curtails leptin and insulin signalling

19

What does the IRS-2 KO mouse display?

neuronal resistance to leptin and insulin

20

What is SOCS3?

a suppressor of cytokine signalling

21

What does SOC3 do?

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

22

What is associated with induction of SOCS3 in the hypothalamus?

leptin resistance

23

How does SOCS3 negatively regulate insulin signalling?

reduced IRS-mediated signalling

24

What else is considered to be contributors to hypothalamic resistance?

SHP2
Hyperleptinemia
ER stress
Inflammation

25

What are some previous drugs for treatment of obesity?

Noradrenergics - CV side effects, appetite suppressants
Serotonergics - appetite suppressants on 5-HT system

26

What was the problem with Sibutramine?

strokes and cardiovascular side effects

27

How did Orlistat work?

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

28

What is the problem with orlistat?

need supplements, can cause cramping and diarrhoea

29

What is signifcant about CB1 KO mice?

have decreased appetite and are lean

30

What is the issue with Rimonabant?

caused sever depression and anxiety and increased risk of suicide

31

What is Larcaserin?

5HT2c receptor agonist

32

What is Qsymia?

combination therapy - topiramate with phentermine - dosage reduced for approval

33

What is Contrave?

combination of opioid antagonist and dopamine uptake inhibiter - CV issues

34

What is Contrave?

combination of opioid antagonist and dopamine uptake inhibiter - CV issues

35

What is the most effective obesity treatment?

Bariatric Surgery

36

Why is Bariatric surgery so effective?

high level of resolution of T2DM
may affect peptide secretions