Upload
morgan-burke
View
218
Download
3
Tags:
Embed Size (px)
Citation preview
signal transduction pathways involved in the regulation of food intake or
why does Homer Simpson loves to eat an excess of donuts
signal transduction pathways involved in the regulation of food intake or
why does Homer Simpson loves to eat an excess of donuts
Regulation of food intake; a complex circuitry between different areas of the brain
SignaltransductionSignaltransduction
With respect to regulation, a general distinction is made between homeostatic (metabolite input) and hedonic regulation
(reward input)
Remember that warm blooded animals, with highly developed brains, have two big worries; how to keep warm and how to keep the brain turning over
A simplified version of homeostatic regulation of food intake; focus on signals from the digestive system (ghrelin, CCK, PYY), adipose tissue (leptin) and the pancreas (insulin)
Nature of the different hormones and neurotransmittor
CCK, cholecystokinin (P06307) (chole=bile, cysto=pouch, kinin=move the bile bladder) is a peptide hormone produced in the small intestine in response to feeding. It causes the release of digestive enzymes from the (exocrine) pancreas, bile from the galbladder and release of H+ in parietal cells of the stomach. In the central nervous system it acts as an anorexigen (hunger suppressant).PYY, peptide tyrosine-tyrosine (P10082) , released by by cells in the ileum and colon in response to feeding and acts as an anorexigenInsulin, (P01308) peptide hormone released by -cells in the islet of Langerhans of the (endocrine) pancreas (hence its name insulin) in response to elevated levels of blood glucose. It acts as an anorexigen. Leptin, (P41159) peptide hormone released by adipose tissue in response to triglyceride loading. Mice lacking the peptide or its receptor are obese. Leptin comes from leptos, meaning thin.
Ghrelin, (Q9UBU3) is a polypeptide hormone produced by cells lining the fundus of the stomach and en by epsilon cells of the pancreas. It has an orexigenic effect (stimulates food intake. It is also produced in the arcuate nucleus where it stimulates secretion of growth hormone by the anterior pituitary gland, hence its name Ghre meaning growth
ghrelin signals hunger (orexigen, stimulates food intake), whereas
leptin, insulin, CCK and PYY signal satiety (anorexigen, inhibit
food intake).
Their targets are neurons in the
arcuate nucleus, of which POMPC/CART
provide an orexic signal and AgRP/NPY
neurons drive the anorexic response
NTS, nucleus tractus solitarius
Neuro-anatomy of homeostatic regulation of food intake; opposing actions of AgRP/NPY and POMC/CART containing neurons
Nature of neurotransmitters involved in homeostatic regulation of food intake
CART, cocaine and amphetamine regulated transcript (Q16568) , discovered as a cocaine- and amphetamine-inducible gene, propeptide, converted by prohormone convertase into at least two active peptides (CART 55-102 and CART 62-102)POMC, pro-opiomelanocortin (P01189) , precursor peptide, converted by prohormone convertases, yielding as many as 10 active peptides amongst which and -MSH (melanocortin) but also -endorphine, hence its name (voir ressource 08, à partir de page 28 (section troisième transit); « vers la voie de la sécrétion contrôlée »)NPY , neuropeptide Y (P01303) , short neuropeptide isolated from the hypothalamus and resembling peptide YY produced by the digestive tract, hence its name. AgRP, agouti-related protein (O00253) , sequence similarity with Agouti signalling peptide, a hormone that controls coat pigmentation in Augoutis (rodents). Acts as an antagonist of the melanocortin-3 and -4 receptor (blocks action of -MSH)
Neuro-anatomy of hedonic regulation of food intake; reward (or pleasure) seeking areas of the brain control orexigenic neurons of LHA
Neurotransmittors involved in hedonic regulation of food intake
Dopamine, tyrosine-derived neurotransmitter
endocannabinoids , -anandamide (arachidonoyl ethanolamide, AEA) (meaning “bliss”), binds CB1 and CB2-2-arachidonoyl glycerol (2-AG)-2-arachidonoyl glyceryl ethere (noladin ether), binds CB1 anb CB2-N-arachidonoyl –dopamine (NADA), binds CB1-Virodhamine (O-arachidonoyl-ethanolamine, OEA), binds CB1 and CB2
endogenous opioids,-enkephalin short peptide cleaved from proenkephalin protein (act on - and -receptor)examples tyr-gly-gly-phe-leu (leu-enkephalin) or tyr-gly-gly-phe-met (met-enkephalin)-endorphins, short peptides cleaved from pro-opiomelanocortin protein (act on -receptor-dynorphin short peptide cleaved from prodynorphin protein (act on -receptor
GABA, -aminobutyric acid, amino-acid derived neurotransmitter
anandamide
So what’s wrong with obese people?
BMI = weight (kg)/height (m)2
-In most cases a polygenic disorder which still has to be understood further-In some (severe) cases a lack of MC4-R signalling, an excess of ghrelin, a lack of leptin or a dysfunctioning of insulin signalling-In some cases a disorder associated with a syndrome such as Prader-Willi, Bardet-Biedl or Alstrôm
30
30
BMI body mass index(IMC indice de masse corporelle)
In the following lectures we will look into more detail how insulin, leptin and ghrelin signal in the arcuate nucleus
Receptor tyrosinekinase (insulin)
Cytokine receptor (leptin)
7 TM receptor (ghrelin)