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Diabetes and metabolic disease BMSc > The hypothalamus-neuropeptides and central circuits (Prof Ashford) > Flashcards

The hypothalamus-neuropeptides and central circuits (Prof Ashford) Flashcards

1
Q

Are monogenic disorders causing obesity common or rare

A

Rare

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2
Q

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

A

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

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3
Q

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

A

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

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4
Q

What centre of the CNS is mainly responsible for obesity

A

Hypothalamus

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5
Q

Where in the hypothalamus would a lesion cause obesity

A

Ventromedial hypothalamus

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6
Q

Where in the hypothalamus would a lesion cause leanness

A

Lateral hypothalamus

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7
Q

What is the blood brain barrier of the hypothalamus

A

Median eminence

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8
Q

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

A

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

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9
Q

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

A

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

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10
Q

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

A

Short term feeding

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11
Q

What do monoamines do to feeding

A

Noradrenaline, dopamine and serotonin all supress food intake

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12
Q

Examples of orexigenic molecules

A

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

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13
Q

Examples of anorexigenic molecules

A

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

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14
Q

How many amino acids does NPY have

A

36

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15
Q

Where particularly are NPY molecules situated

A

The ARC and DMN

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16
Q

List the 6 main parts of the hypothalamus

A

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

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17
Q

When is NPY gene expression increased/decreased?

A

Increased on fasting and reduced after feeding

18
Q

What effect does NPY have on weight and lipogenesis

A

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

19
Q

What is an example of one of the melanocortins

A

Alpha-MSH (alpha melanocyte stimulating hormon)

20
Q

What gene codes alpha-MSH

A

POMC gene (proopiomelanocortin)

21
Q

When is the POMC gene expression reduced/increased

A

Reduced on fasting and increased following attainment of positive energy balance

22
Q

Where particularly are alpha-MSH levels high in the brain

A

ARC

23
Q

What is alpha-MSH effect on food intake

A

Inhibits food intake

24
Q

Which two melanocortin receptor subtypes are expressed in the brain

A

MC3 and MC4

25
Q

Describe first order neurons journey for NPY and POMC neurons

A

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

26
Q

What is agouti-related protein

A

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

27
Q

What does CART stand for

A

Cocaine and amphetamine regulated transcript

28
Q

Where is CART found particularly in the brain

A

ARC, VMH and PVN

29
Q

Which part of the hypothalamus regulates TRH and PVN

A

The PVN

30
Q

What does TRH (thyrotropin recpetor hormone) do

A

Stimulates release of TSH and prolactin

31
Q

What actions does CRH have

A

Reduces food intake, increased sympathetic outflow and increased energy expenditure

32
Q

How many amino acids does MCH have

A

19

33
Q

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

A

Peptides controlling sleep cycles and central injection increases food intake

34
Q

What is the short version of the agouti analogue

A

AgRP

35
Q

How does agouti antagonise MSH?

A

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

36
Q

What are 5 signals that inform the body of satiety

A

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

37
Q

Info on CCK

A

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

38
Q

Info on PYY 3-36

A

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

39
Q

Info on GLP-1

A

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

40
Q

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

A

An endocrine response to the pituitary and the autonomic preganglionic neurons

41
Q

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

A

Behavioural response (cortex) and autonomic preganglionic neurons

Diabetes and metabolic disease BMSc (9 decks)

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