Obesity lecture

Question 1

model of neurohormonal control

Answer 1

more tolerant to weight gain than weight loss

Question 2

hunger center in brain

Answer 2

lateral hypothalamus

Question 3

satiety center in brain

Answer 3

ventromedial hypothalamus

Question 4

if lateral hypothalamus is lesioned, mouse is _______.

if ventromedial hypothalamus is lesioned, mouse is _______.

Answer 4

starving

obese

Question 5

job of leptin

Answer 5

decrease food intake, increase energy expenditure

Question 6

POMC cart neurons

Answer 6

anorexigenic. when stimulated, decrease feeding

Question 7

AgRP NPY neurons

Answer 7

orexigenic. when stimulated, they increase feeding

Question 8

POMC neurons release ______

Answer 8

alpha MSH

Question 9

Leptin’s effect on POMC and AgRP neurons

Answer 9

leptin will excite/ depolarize POMC neurons and inhibit AgRP neurons

Question 10

insulin’s effect on POMC neurons

Answer 10

insulin depolarizes POMC neurons to decrease feeding

Question 11

ghrelin is the _____ signal

leptin is the _____ signal

Answer 11

hunger

satiety

Question 12

PYY

Answer 12

a satiety signal

inhibits AgRP signaling

Question 13

effect of CCK

Answer 13

will amplify satiety signals by acting at NTS… this is one of the effects of the anorexigenic pathway

Question 14

effect of leptin resistance on sympathetics and fat metabolism

Answer 14

will cause impaired sympathetic activity.

hyperleptinemia, increase lipogenesis, decrease lipolysis, decrease thermogenesis

Question 15

leptin and insulin effect on VTA signaling

Answer 15

inhibit dopamine signaling in the VTA (stops the reward feeling)

Question 16

ghrelin effect on VTA signaling

Answer 16

increase firing rate of the DA neurons in the VTA

Question 17

POMC neurons and the lateral hypothalamus

Answer 17

POMC neurons normally are an anorexigenic signal. but to the lateral hypothalamus, its an orexigenic pathway…
when depolarized, POMC neurons dampen the signal to the lateral hypothalamus.

Question 18

Norepinephrine effect on feeding

Answer 18

in PVN: NE stimulates feeding

in perfornical area: NE reduces feeding

Question 19

Serotonin effect on feeding

Answer 19

5-HT decreases meal size and duration, decreases rate of feeding, decreases carbohydrate intake
5-HT pretreatment blocks NE-induced feeding from the PVN

Question 20

sympathomimetic amines

Answer 20

• Phentermine
• Benzphetamine
• Diethylproprion
• Phendimetrazine
  phentermine + Topiramate = qysmia (SE: paresthesia )

MOA: reduce appetite by eliciting NE release & modulating catecholamine systems

Question 21

mutations of which receptor are ~ 5% more present in obese individuals

Answer 21

MCR4

Question 22

Orlistat

Answer 22

what is it: pancreatic & gastric lipase inhibitor

MOA: decreases fat absorption

side effects: flatulance with discharge, oily spotting, fecal urgengy

loss: ~ 3 kg

Question 23

Lorcaserin

Answer 23

what is it: 5-HT 2C agonist

MOA: works on POMC neurons, pomc n release alphaMSH, activates satiety center (more full)

side effects: cardiac valvulopathy, risk of serotonin syndrome

loss: ~ 3 kg

Question 24

Bupropion/ Naltrexone

Answer 24

appetite suppressant
acts on the hypothalamic-melanocortin system & the mesolimbic reward system
Beta endorphins released from POMC neurons have an auto-inhibitory feedback effect on POMC neurons.

Naltrexone blocks this effect, so there is no inhibitory feedback and POMC continues to signal

side effect: nausea (black box warning about suicide)
loss: ~ 4-5 kg loss

Question 25

Liraglutide

Answer 25

GLP-1 agonist

MOA: delays gastric emptying, food in stomach longer

loss: 5.8 kg

Question 26

Zonisamide

Answer 26

antiepileptic drug
3.3 kg loss
zonisamide + olanzapine prevented weight gain normally seen with olanzapine

Question 27

Metformin

Answer 27

antihyperglycemic

Question 28

Exenatide

Answer 28

antihyperglycemic - stimulates glucose dependent insulin secretion
delays gastric emptying
5.1 kg loss

Question 29

pramlinitide

Answer 29

antihyperglycemic
amylin analog, delays gastric emptying
causes weight loss

Question 30

Canagliflozin, dapagliflozin, empagliflozin

Answer 30

SGLT-2 inhibitors
MOA: urinary loss of glucose, less glucose is being absorbed and stored –> weight loss

2-4 kg weight loss in diabetic patients

Question 31

adjustable gastric banding procedure

Answer 31

makes small stomach pouch, smaller stomach capacity, lower food intake

Question 32

sleeve gastrectomy

Answer 32

portion of the stomach is excised.
stomach left looking tubular.
less space for food

Question 33

Roux-en-Y gastric bypass

Answer 33

excise part of the stomach and link stomach to jejunum.
bypasses the duodenum
most common bariatric surgery. less food is eaten, less is absorbed.

Question 34

biliopancreatic diversion (BPD)

Answer 34

aka duodenal switch
- part of stomach is excised, and stomach is rerouted to the most distal part of SI (ilium)
- food is basically rerouted to the colon
most invasive

Question 35

if excess PNS outflow is removed

Answer 35

weight gain associated with MCR4 mice is significantly reduced

Question 36

Neuropeptide Y effect on feeding

Answer 36

if injected with NpY, rat continues eating even when full

• causes preference for carbs
• NpY prevalent in both PVN and perfornical area

Question 37

Galanin effect on feeding

Answer 37

• galanin found in paraventricular hypothalamus
• injection of galanin caused increase in food intake
• caused preference for fats vs carbohydrates

Question 38

nicotine for weight loss

Answer 38

nicotine is an appetite suppressant

- these effects mediated by alpha 4 beta 2 (a4b2) receptor.