Wee 11 - Hypothalamic control Flashcards
where are the hypothalamus and pituitary?
diancephalon
hypothalamus control centers
It is crucial to the control of feeding, plasma osmolality, body temperature, and sexual and stress responses.
That control always involves negative feedback, i.e. processing chemical and neural signals from the body to monitor how well things are working and to detect disturbances.
Some control systems maintain homeostasis — keeping some aspect of the internal environment (e.g. osmolality) roughly constant despite disturbances. Other control systems vary things through time, e.g. in circadian rhythms.
how does the hypothalamus exert its influence neurally and hormonally
Nuclei within the hypothalamus send neural signals to each other and to other parts of the brain.
The hypothalamus also synthesizes hormones which it transports
down axons to the posterior lobe of the pituitary, where they are
released into the blood.
And the hypothalamus makes releasing hormones that travel
through capillaries (the hypophyseal portal system) to the anterior
pituitary, where they trigger the release into the blood of other
hormones, made in the pituitary.
when do mice become obese
when they have lesions in the ventromedial hypothalamus
what do mice become thin
when they have lesions in the lateral hypothalamus
what are the ventromedial and lateral hypothalamus controlled by?
two groups of neurons in the arcuate nucleus of the hypothalamus: arcuate NPY cells drive feeding while arcuate POMC inhibit feeding
what happens in the fasting state
arcuate NPY neurons encourage feeding.
They release neuropeptide Y (NPY), GABA, and in some cases also agouti-related peptide (AgRP)
what does Arc NPY inhibit
Signals from Arc NPY cells inhibit neurons in the periventricular nucleus, a satiety or anorexigenic center that quells appetite for food.
PVN usually excites the sympathetic nervous system, but Arc NPY acts via PVN to decrease sympathetic activity.
High sympathetic activity usually inhibits feeding, but because Arc NPY inhibits sympathetic activity, it disinhibits feeding behavior.
what does Arc-NPY excite
it excites neurons in the lateral hypothalamus, a feeding centre. Projections from LH release orexin at their synapses, inhibiting PVN and stimulating feeding behaviour.
what happens in the postprandial state?
arcuate POMC neurons inhibit feeding. they are a group of neurons in the arcuate neurons containing pro-opiomelanocortin.
they cleave POMC to make alpha-melanocyte stimulating hormone which they release at their synapses.
what does alpha-melanocyte stimulating hormone excite
neurons in the PVN and the ventromedial nucleus.
this excites the sympathetic nervous system.
what does alpha melanocyte stimulating hormone inhibit
neurons in the dorsomedial hypothalamus.
Activity in DMH usually inhibits the sympathetic nervous system, but Arc POMC inhibits DMH, so the net result is that sympathetic activity is disinhibited (increased)
what does combined excitation and inhibition by alpha melaocyte stimulating hormone cause
stron inhibition of feeding
what is Arc POMC excited and inhibited by
excited by the sympathetic nervous system (+ve feedback loop) and inhibited by Arc NPY
how does control of feeding work
works based on negative feedback, on signals that tell the control center how close the system is to some goal state, or set point
set points in rats with lesions
rates with VMH lesions dont get fatter and fatter forever, but level off at a new set point above their original weight and rats with LH lesions level off at a new low-set point.
how does hypothalamus infer body weight
leptin levels
leptin
protein released into the blood mainly by fat cells, so the more fat you have, the more circulating leptin
leptin receptors
some cells in the body have membrane receptors for leptin, including cells in the feeding and anorexigenic centers of the hypothalamus.
what causes obesity
mutations in the genes that produce leptin or the leptin receptor cause obesity in mice and humans
what does leptin inhibit and excite - Arrc-NPY
leptin inhibits feeding centers Arc-NPY and LH and excites PVN which boosts sympathetic activity inhibiting feeding
what does leptin inhibit and excite - Arc-POMC
it inhibits DMH and excites Arc POMC and VMH (boosting sympathetic activity)
how does brain known when to end a meal
not from leptin - beacuase it is too slow
through blood glucose; it increases as you eat, and its rising level excites Arc POMC and inhibits LH, inhibiting further feeding
other mechanisms involve sensors in the wall of the stomach and intestines that measure nutrients and stretch, and response by releasing hormones that act on the hypothalamus
postprandial state - gut hormones
inhibit feeding
sensors in the wall of the small intestine detect stretch, sugar and protein, leading to the release of cholecystokinin (CCK), peptide YY, and glucagon like petide 1\
in fasting what is released from the stomach
ghrelin released from the stomach encourages feeding
it is released into the blood by cells in the stomach wall when the stomach is empty stretching the stomach stops ghrelin release
what does ghrelin act on
it acts directly on Arc-NPY and LH (exciting them) and on PVN (inhibiting it)
rimonabant
blocks CB1 endocannabinoid receptors, can lead to moderate weight loss, but causes depression, major weight loss and suicide
amphetamines and fenfluramine
an anti obesity drug withdrawn in 1997 because of cardiovascular side effects
leptin as a drug
rarely helps, because fewer than 1% pf humans with morbid obesity are leptin-deficient.
CCK and PPY agonists
not much success
liraglutide
GLP1 agonist, works better
