15 - Appetite Regulation Flashcards
Arcuate nucleus
Main centre for appetite regulation (in the hypothalamus)
NPY/Agouti related peptide
Laterally
Appetite stimulating
Cocaine related transcript (CART) and pro opiomelanocortin (POMC)
Medially
Appetite inhibiting
Where is agouti found
Controls hair colour
AgRP found in the hypothalamus hypothalamus co-current with cells producing NPY
Function of agouti
Acts as a melanocortin receptor antagonist
What drops AgRP levels
Leptin
Insulin
Orexigenic (Appetite stimulating) factors
Peripheral - Ghrelin
Central - MHC, AgRP, NPY
Anorexigenic (Appetite inhibiting) factors
Central - POMC, CART, 5-HT
Peripheral - PYY, GLP-1, Leptin, Insulin, CCK
POMC control
POMC –> Melanocortin –> Binds to melanocortin receptor (MCR-4) –> Controls energy balance
POMC deficient
Develop hyperphagia and obesity
Deletion of MC4R
Hyperphagia
Mutation in 4-5% of obese
5% cause of childhood obesity
Effect of serotonin on appetite
5-HT is anorexigenic
What receptors does 5-HT act on in appetite regulation and the function
Htr1b and Htr2c
- increase signalling from POMC neurons (Htr2c)
- decrease AgRP neuron signalling (Htr1b)
What does ghrelin stimulate + where is it released
NPY neurons to increase appetite
Stomach
Where are ghrelin receptors
Vagus nerve
stomach
What type of release is ghrelin released n
Circadian release
Where is GLP-1 released and what secretes it
L cells secrete in the ileum
Function of GLP-1
Decreases appetite by stimulating insulin and POMC and inhibits NPY
Function of PYY 3-36
Inhibits NPY and stimulates POMC
Like glp-1
Antagonises ghrelin
Pathway of PYY 3-36
PYY 3-36 synthesised in the gut
reaches hypothalamus via blood
PYY inhibits NPY neurons via Y2 receptor and stimulates POMC neurons
Food intake declines
Where is cholecystokinin released
CCK is secreted from I-type enteroendocrine cells in the duodenum/jejunum in the presence of fat
Function of CCK
Acts to supress appetite
Reduce gastric emptying
Stimulate production of bile + contraction of GB + stimulate enzymes to digest fat
What mutation do the Otsuka Long-Evans Tokushima Fatty rats hae
Mutations in CCK-A (cck receptor)
obese and t2d
Where is leptin secreted from
Adipose tissue (fat cells)
What is leptin release
Circadian release
Function of leptin
Inhibits NPY and AgRP
Genetic defects of leptin
Defective leptin - ob
Defective leptin receptor - db or zucker rat
Phenotype of ob/ob and db/db mice
Obese Increased appetite Diabetes Overexpression of NPY, AGRP Decreased expression of POMC
What can leptin injections treat
Leptin deficient children
reduces body weight and fat mass
Leptin resistance
Caused by loss of function mutations in the leptin receptor
therefore leptin administration has little effect
What is lipodystrophy
Selective loss of body fat
low leptin levels
What forms malonyl coa
from excess acetyl-coA to synthesis FA
What controls levels of Malonyl coA
AMPK (Phosphorylation of synthesise enzymes)
+ calcium regulated with ghrelin?
What does malonyl COa INHIBIT
the carnitine shuttle
so no breakdown of fat/triglycerides
Cannabinoids on appetite
Increase appetite
CB1 receptors in hypothalamus increases palatability of food
