Endo 14 - Endocrine control of food intake

Question 1

Bodyweight homeostasis can be influenced by?

Answer 1

1. Ghrelin, PYY, other gut hormones
2. Neural input from periphery and other brain regions
3. Leptin

Question 2

The paraventricular nucleus is a source of?

Answer 2

TRH

Question 3

Where is the arcuate nucleus located

Answer 3

Either side of the 3rd ventral, above the median eminence

Question 4

The arcuate nucleus is a key area in integrating peripheral and central feeding signals. How does it achieve this

Answer 4

Arcuate nucleus - has incomplete blood brain barrier - allows access to peripheral hormones

Arcuate nucleus has 2 neuronal populations - these neurones extend to other hypothalamic and extrahypothalamic regions:

1. Stimulatory (appetite): NPY/Agrp neuron
2. Inhibitory (appetite): (POMC neuron)

Question 5

Explain the melanocortin system of food intake

Answer 5

MC4R on Paraventricular nucleus = decreases food intake

POMC neurones secrete a-MSH which stimulates MC4R - decreases food intake

Agrp neurones secrete agrp which inhibits MC4R - increases food intake

Question 6

What are the rare human CNS mutations that affect appetite

Answer 6

POMC and MC4R deficiency found - they cause morbid obesity

No NPY/Agrp mutations discovered in humans

Question 7

Describe leptin

How does leptin work?

Answer 7

Leptin - released from white adipose tissues- hence release is proportional to fat mass

Leptin receptors in hypothalamus (Ob-R)

Ob gene codes for leptin

It signals to the brain that there is enough fat - decreases food intake and increases thermogenesis

It activates POMC and inhibits NPY/Agrp neurones

Question 8

Why is leptin ineffective as a weight control drug?

Answer 8

Most obese humans have high levels of leptin - so leptin resistance occurs.

Leptin present but doesn’t signal effectively

Question 9

What can leptin absence cause

Answer 9

Hyperphagia (constant starving), lower energy expenditure, sterility

Giving leptin in these circumstances reduces obesity and may also restore LH/FSH pulsatility

Question 10

What is the role of insulin in food intake

Answer 10

1. Insulin = circulates at levels proportional to body fat
2. Receptors in hypothalamus
3. Central insulin administration reduces food intake

Question 11

The GI releases more than …. different regulatory peptide hormones

Answer 11

20

GIT = largest endocrine organ

Question 12

Ghrelin is known as the hunger hormone. How come?

Answer 12

It increases food intake by:

1. Stimulates NPY/Agrp neurones
2. Inhibits POMC neurones

Question 13

Which type of cells secrete PYY and GLP-1?

Answer 13

L cells

secretory granules near basolateral membrane close to capillary

Question 14

PYY is the satiety hormone. Why

Answer 14

It is released after meals - reduces appetite by:

1. Inhibits NPY release
2. Stimulates POMC neurons
3. Decreases appetite

Question 15

What gene codes for glucagon like peptide 1 (GLP-1) and when is GLP1 released

Answer 15

Coded for by Preproglucagon gene

GLP-1 is a gut hormone released after eating (post prandially)

Question 16

GLP-1 is an incretin. What is an incretin

Answer 16

Incretins = hormones that:

1. Released after eating
2. Stimulate insulin secretion from B-islet cells in pancreas

GLP-1 is mimicked to treat T2DM (GLP-1 agonists / DPP-4 inhibitors) - DPP4 breaks down GLP-1

Question 17

What is the GLP-1 analogue used that is long acting

Answer 17

Saxenda (liraglutide)

Double the dose used for T2DM

Question 18

Thrifty gene hypothesis - explain

Answer 18

Basically, in cavemen times it was better to have fat storage as famines and stuff happened. But now we don’t need to run around to catch food etc so it predisposes to obesity. Thin humans didn’t survive famines so couldnt pass genes

Question 19

Adaptive Drift gene hypothesis - explain

Answer 19

Normal distribution of weight - because fat people were eaten and thin people didn’t survive

Humans also learned to defend themselves against predators - so obesity wasn’t selected against
as fat people could defend themselves

Putting on body fat then became a neutral change - dint affect chances of survival so much

Question 20

Leptin and insulin signal long term food intake. What signals to regulate short term food intake

Answer 20

GIT