The hypothalamus-neuropeptides and central circuits (Prof Ashford)

Question 1

Are monogenic disorders causing obesity common or rare

Answer 1

Rare

Question 2

Why is it harder to lose weight when obesity is maintained for a long period

Answer 2

Body defends new weight as brain believes this is a normal weight

Question 3

What are the three main ways the CNS influences energy balance and body weight (brief description with it)

Answer 3

1) Behaviour (feeding and exercise)
2) ANS activity (regulates energy expenditure)
3) Neuroendocrine system (secretion of hormones)

Question 4

What centre of the CNS is mainly responsible for obesity

Answer 4

Hypothalamus

Question 5

Where in the hypothalamus would a lesion cause obesity

Answer 5

Ventromedial hypothalamus

Question 6

Where in the hypothalamus would a lesion cause leanness

Answer 6

Lateral hypothalamus

Question 7

What is the blood brain barrier of the hypothalamus

Answer 7

Median eminence

Question 8

What are the effects of glutamate on food intake and body weight

Answer 8

NMDA injected into LHA stimulates short term feeding (less than 10 mins)

Question 9

What are the effects of GABA on food intake and body weight

Answer 9

Injection of muscimol (GABAa receptor agonist) into VMN, PVN or DMN stimulates feeding (around 30 mins)

Question 10

What are the effects of opioids on food intake and body weight

Answer 10

Short term feeding

Question 11

What do monoamines do to feeding

Answer 11

Noradrenaline, dopamine and serotonin all supress food intake

Question 12

Examples of orexigenic molecules

Answer 12

NPY, galanin, MCH, orexins, agouti, ghrelin and endocannabinoids

Question 13

Examples of anorexigenic molecules

Answer 13

Leptin, insulin, alpha-MSH, CART, GLP-1, TRH, CRH and PYY 3-36

Question 14

How many amino acids does NPY have

Answer 14

36

Question 15

Where particularly are NPY molecules situated

Answer 15

The ARC and DMN

Question 16

List the 6 main parts of the hypothalamus

Answer 16

Para-ventricular nucleus, dorsomedial nucleus, perifornical area, ventromedial nucleus, arcuate nucleus and lateral hypothalamic area

Question 17

When is NPY gene expression increased/decreased?

Answer 17

Increased on fasting and reduced after feeding

Question 18

What effect does NPY have on weight and lipogenesis

Answer 18

It is orexigenic (eat more), it reduces energy expenditure and induces lipogenic enzymes in fat and liver cells

Question 19

What is an example of one of the melanocortins

Answer 19

Alpha-MSH (alpha melanocyte stimulating hormon)

Question 20

What gene codes alpha-MSH

Answer 20

POMC gene (proopiomelanocortin)

Question 21

When is the POMC gene expression reduced/increased

Answer 21

Reduced on fasting and increased following attainment of positive energy balance

Question 22

Where particularly are alpha-MSH levels high in the brain

Answer 22

ARC

Question 23

What is alpha-MSH effect on food intake

Answer 23

Inhibits food intake

Question 24

Which two melanocortin receptor subtypes are expressed in the brain

Answer 24

MC3 and MC4

Question 25

Describe first order neurons journey for NPY and POMC neurons

Answer 25

Start of the the ARC (arcuate nucleus) and then travel to the PVN and LHA/PFA

Question 26

What is agouti-related protein

Answer 26

A coat colour regulating agent that antagonises the action of alpha MSH on MC receptors

Question 27

What does CART stand for

Answer 27

Cocaine and amphetamine regulated transcript

Question 28

Where is CART found particularly in the brain

Answer 28

ARC, VMH and PVN

Question 29

Which part of the hypothalamus regulates TRH and PVN

Answer 29

The PVN

Question 30

What does TRH (thyrotropin recpetor hormone) do

Answer 30

Stimulates release of TSH and prolactin

Question 31

What actions does CRH have

Answer 31

Reduces food intake, increased sympathetic outflow and increased energy expenditure

Question 32

How many amino acids does MCH have

Answer 32

19

Question 33

What are orexins and what does central injection do to food intake

Answer 33

Peptides controlling sleep cycles and central injection increases food intake

Question 34

What is the short version of the agouti analogue

Answer 34

AgRP

Question 35

How does agouti antagonise MSH?

Answer 35

By reverse agonism (binds to the same receptor as agonist but has an opposite effect)

Question 36

What are 5 signals that inform the body of satiety

Answer 36

CCK, PYY 3-36, GLP-1, oxyntomodulin (OXM) and obestatin

Question 37

Info on CCK

Answer 37

Enteroendocrine cells in the gut that signal to the hindbrain (NTS)

Question 38

Info on PYY 3-36

Answer 38

From L-cells in the gut which inhibit gastric motility and reduces food intake

Question 39

Info on GLP-1

Answer 39

From L-cells that inhibit gatsric emptying and reduce food intake

Question 40

What are the two main anorexigenic pathways that come from the PVN

Answer 40

An endocrine response to the pituitary and the autonomic preganglionic neurons

Question 41

What are the two main orexigenic pathways that come from the LHA/PFA

Answer 41

Behavioural response (cortex) and autonomic preganglionic neurons