Hormonal regulation of appetite and satiety (week 7) Flashcards
how does CNS influence energy balance and body weight
By:
- behaviour - feeding physical activity
-ANS activity - regulates energy expenditure
-neuroendocrine system - secretion of hormones
orexigenic
increase food intake
decrease energy store
decrease energy expenditure
anorexigenic
decreased food intake
increase energy store
increase energy expenditure
hypothalamic regulation - appetite and satiey
feedback regulation:
-signals produced in response to body nutritional status
-signals detected by the hypothalamus
-act to modulate food intake and energy expenditure
Body weight and food intake are also regulated by long-term processes e.g.,adiposity signals. What are these signals ?
Leptin
Insulin
Adiponectin
Ghrelin
Resistin
what are some orexigenic peptide hormones
NPY
Galanin
MCH
Orexins
Agouti
Ghrelin
Endocannabinoids
what are some anaorexigenic peptide hormones
Leptin
Insulin
a-MSH
Cart
GLP-1
TRH
CRH
PYY
what is aMSH
a melanocyte stimulating hormone formed by sequential cleavages of the proopiomelanocortin (POMC) precursor polypeptide
what is POMC
Pro-opiomelanocortin, a precursor protein processed to produce various peptide hormones. Produced in the pituitary gland.
where are aMSH levels high
in the hypothalamus and this peptide inhibits food intake (anorexigenic)
what are melanocortin receptor subtypes
MC-3 and MC-4, mainly expressed in the brain. Synthetic agonist and antagonists to these suppress and enhance food intake respectively
what does deletion of MC-4 or MC-3 do
causes obesity in mice
explain neuropeptide y (NPY)
a 36 aa peptide; one of the most abundant in the human brain
injection of NPY into hypothalamus potently stimulates food intake and reduces energy expenditure (orexigenic)
repeated administration can lead to obesity
mice lacking NPY receptor subtypes, Y1 or Y5 pre-disposed to obesity
agouti-related protein (AgRP)
AgRP co-expresses with NPY in ARC neurons
AgRP and Agouti (Ay) are antagonists to MC3 and MC4 receptors
Intracerebroventricular (ICV) AgRP causes long lasting hyperphagia (Orexigenic)
adiposity signals - leptin
member of the cytokine family, 146 aa long, made and secreted from adipocytes
circulates in proportion to fat mass
high levels of leptin receptors (Ob-Rb) expressed on ARC hypothalamic neurons
ICV leptin inhibits food intake and decreases body weight of rodents
neuron specific deletion of leptin receptor (Ob-Rb) results in obesity
biological roles of leptin
bone formation
tumorigenesis
angiogenesis
maintenance of reproductive system
maintenance of immune system
peripheral glucose homeostasis/ insulin sensitivity
adiposity signals- insulin
circulates in proportion to adiposity
transport system for insulin to enter brain
high levels of insulin receptors expressed in hypothalamus most notably in the ARC
ICV insulin inhibits food intake and decreases body weight of rodents
cholecystokini
site of secretion- enteroendocrine cells of deodenum and jejumen
stimulus - released in proportion to lipids and proteins in meals
action - signals via sensory nerves to hindbrain and stimulates hindbrain directly (nucleus of solitary tract - NTS)
peptide yy (PPY 3-36)
site of secretion - endocrine mucosal L-cells and G-I tract
Stimulus - Levels increase rapidly post-prandially
action - Inhibits gastric motility, slows emptying reduces food intake (hypothalamus)
glucagon-like peptide 1 (GLP-1)
site of secretion - Lcells of G-I tracts (product of pro-glucagon gene)
stimulus - levels increase in response to food ingestion
action - inhibits gastric emptying and reduces food intake (hypothalamus and NTS)
Oxyntomodulin (OXM)
Site of secretion - Oxyntic and L-cells of small intestine (produce of pro-glucagon gene)
stimulus - released after a meal
action - acts to supress appetite - mechanism and site unclear
Obestatin
site of secretion - cells lining the stomach/ small intestine (peptide from gene encoding ghrelin)
stimulus - release in response to ingestion
action - reduces food intake (may act to antagonise ghrelin)
agouti and obesity
gene encodes a small protein - AGOUTI - natural antagonist of the melanocortin 1 (MC- 1) receptor in melanocytes - responsible for hair colour
mutation results in gene rearrangement causing ubiquitous ectopic expression
Ay mutation leads to obesity
Ay also anatogonist for hypothalamic MC-4 receptor - this is the cause of obesity in this mouse model
what Is JAK2-STAT used in
transcriptional regulation eg. SOCS3 and POMC
