The hypothalamus-neuropeptides and central circuits (Prof Ashford) Flashcards
Are monogenic disorders causing obesity common or rare
Rare
Why is it harder to lose weight when obesity is maintained for a long period
Body defends new weight as brain believes this is a normal weight
What are the three main ways the CNS influences energy balance and body weight (brief description with it)
1) Behaviour (feeding and exercise)
2) ANS activity (regulates energy expenditure)
3) Neuroendocrine system (secretion of hormones)
What centre of the CNS is mainly responsible for obesity
Hypothalamus
Where in the hypothalamus would a lesion cause obesity
Ventromedial hypothalamus
Where in the hypothalamus would a lesion cause leanness
Lateral hypothalamus
What is the blood brain barrier of the hypothalamus
Median eminence
What are the effects of glutamate on food intake and body weight
NMDA injected into LHA stimulates short term feeding (less than 10 mins)
What are the effects of GABA on food intake and body weight
Injection of muscimol (GABAa receptor agonist) into VMN, PVN or DMN stimulates feeding (around 30 mins)
What are the effects of opioids on food intake and body weight
Short term feeding
What do monoamines do to feeding
Noradrenaline, dopamine and serotonin all supress food intake
Examples of orexigenic molecules
NPY, galanin, MCH, orexins, agouti, ghrelin and endocannabinoids
Examples of anorexigenic molecules
Leptin, insulin, alpha-MSH, CART, GLP-1, TRH, CRH and PYY 3-36
How many amino acids does NPY have
36
Where particularly are NPY molecules situated
The ARC and DMN
List the 6 main parts of the hypothalamus
Para-ventricular nucleus, dorsomedial nucleus, perifornical area, ventromedial nucleus, arcuate nucleus and lateral hypothalamic area
When is NPY gene expression increased/decreased?
Increased on fasting and reduced after feeding
What effect does NPY have on weight and lipogenesis
It is orexigenic (eat more), it reduces energy expenditure and induces lipogenic enzymes in fat and liver cells
What is an example of one of the melanocortins
Alpha-MSH (alpha melanocyte stimulating hormon)
What gene codes alpha-MSH
POMC gene (proopiomelanocortin)
When is the POMC gene expression reduced/increased
Reduced on fasting and increased following attainment of positive energy balance
Where particularly are alpha-MSH levels high in the brain
ARC
What is alpha-MSH effect on food intake
Inhibits food intake
Which two melanocortin receptor subtypes are expressed in the brain
MC3 and MC4
Describe first order neurons journey for NPY and POMC neurons
Start of the the ARC (arcuate nucleus) and then travel to the PVN and LHA/PFA
What is agouti-related protein
A coat colour regulating agent that antagonises the action of alpha MSH on MC receptors
What does CART stand for
Cocaine and amphetamine regulated transcript
Where is CART found particularly in the brain
ARC, VMH and PVN
Which part of the hypothalamus regulates TRH and PVN
The PVN
What does TRH (thyrotropin recpetor hormone) do
Stimulates release of TSH and prolactin
What actions does CRH have
Reduces food intake, increased sympathetic outflow and increased energy expenditure
How many amino acids does MCH have
19
What are orexins and what does central injection do to food intake
Peptides controlling sleep cycles and central injection increases food intake
What is the short version of the agouti analogue
AgRP
How does agouti antagonise MSH?
By reverse agonism (binds to the same receptor as agonist but has an opposite effect)
What are 5 signals that inform the body of satiety
CCK, PYY 3-36, GLP-1, oxyntomodulin (OXM) and obestatin
Info on CCK
Enteroendocrine cells in the gut that signal to the hindbrain (NTS)
Info on PYY 3-36
From L-cells in the gut which inhibit gastric motility and reduces food intake
Info on GLP-1
From L-cells that inhibit gatsric emptying and reduce food intake
What are the two main anorexigenic pathways that come from the PVN
An endocrine response to the pituitary and the autonomic preganglionic neurons
What are the two main orexigenic pathways that come from the LHA/PFA
Behavioural response (cortex) and autonomic preganglionic neurons
