Endo 13 - Endocrine Control of Food Intake Flashcards

1
Q

What is the name of the part of the hypothalamus which is involved in the regulation of food intake?

A

Arcuate nucleus

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2
Q

What is a specialised feature of the arcuate nucleus which allows it to integrate central and peripheral inputs?

A

Circumventricular organ

- incomplete blood brain barrier so exposed to peripheral hormones

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3
Q

What are the two neuronal populations in the arcuate nucleus?

A
  1. Agrp/NYP - Stimulatory

2. POMC - inhibitory

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4
Q

Describe how the melanocortin system works

A

Under normal conditions, POMC is broken down into alpha MSH
alpha MSH is a agonist of MC4R and prevents food intake
When you need to eat, Agrp activity will increase, blocking MC4R receptor, therefore increasing food intake

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5
Q

Name two types of mutations which affect the melanocortin system

A
  1. POMC deficiency - associated with pale skin, red hair and obesity
  2. MC4R mutation - associated with obesity
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6
Q

What are the features of the ob/ob mouse?

A
  • obese
  • diabetes
  • infertile
  • decreased energy expenditure
  • decreased body temperature
  • stunted growth
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7
Q

What is leptin?

A

Released from fat and tells the brain how much fat there is in storage so regulated eating

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8
Q

What is the effect of leptin administered centrally on leptin deficient individuals?

A

Decreases foot intake

increases thermogenesis

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9
Q

What effect does leptin have on the melanocortin system?

A

activates POMC and inhibits Agrp neurones so activates MC4R and decreases food intake

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10
Q

Why does leptin treatment not work as an anti-obesity drug?

A

Leptin circulates at levels proportional to fat mass
So obese people have high leptin

high leptin = more resistance

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11
Q

Why won’t people with leptin deficiency go through puberty?

A

Without leptin, GnRH release is stopped

so less LH and FSH so puberty cannot happen

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12
Q

Insulin circulates at levels…

A

that are proportional to body fat

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13
Q

Describe the central effects of insulin

A

reduces food intake
chronic - reduced body fat
acute - reduced intake of sugar

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14
Q

What is ghrelin?

A

Hunger hormone

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15
Q

What organ releases ghrelin?

A

Stomach

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16
Q

What is ghrelin activated by?

A

Ghrelin O Acyltransferase - GOAT

17
Q

What effect does ghrelin have on the melanocortin system?

A

stimulates NPY/Agrp neuones
inhibits POMC
so inhibits MC4R
so increases food intake

18
Q

Which cells of the GI tract release PYY and GLP-1?

A

L- Cells in the distal small intestine

19
Q

When is PYY released?

A

Post meal - depends on size of meal

20
Q

What are the effects of PYY?

A

stimulates POMC neurones so decreases food intake

21
Q

What is the effect of GLP-1?

A

decreases food intake

22
Q

What is the incretin effect?

A

Giving someone oral glucose will achieve a higher spike insulin that if you give the same amount of glucose IV

23
Q

What makes the incretin effect work?

A

glucose travelling in the GI tract potentiates the effect of hormones

24
Q

Describe the degradation of GLP-1?

A

Broken down very quickly - half life of less than 1 min

25
Q

Name a long acting GLP-1 receptor agonist that is used for diabetes and obesity?

A

Saxenda

26
Q

What is the problem with PYY as a drug target?

A

Narrow therapeutic window

causes nausea

27
Q

What are the comorbities associated with obesity?

A

stoke, mi, cancer, diabetes, hypertension

28
Q

What is the thrifty gene hypothesis?

A

evolutionarily sensible to put on weight to survive scarcity

29
Q

What is the adaptive drift hypothesis?

A

used to be normal distribution of weight
predators would kill fat people
but we got better at evading predators

so more likely to put on weight now