1: Hormonal Regulation of Satiety and Hunger

Lateral nucleus

'the feeding center' stimulation leads to hyperphagia

Ventromedial nuclei

'the satiety center' stimulation leads to aphagia.

CCK

Expressed mainly in the duodenum and jejunum. Causes gall bladder contraction, pancreatic enzyme release and inhibits gastric enzyme release. Inhibits AgRP and stimulates POMC/CART

Arcuate nuclei

Multiple hormones converge at this site to regulate eating and energy consumption. Contains anorexigenic and orexigenic neurons which extend to the paraventricular nuclei.

AgRP

a peptide released from the arcuate nucleus in the hypothalamus, it blocks MCR-4 receptors in the PVN and stimulates release of GABA which inhibits POMC. This increases appetite. Inhibited by insulin and CCK.

Neuropeptide Y

a peptide released from the arcuate nucleus in the hypothalamus, it inhibits the paraventricular nuclei via hyperpolarization and leads to increased appetite with preference for carbs. It also reduces fatty oxidation, promotes carb oxidation and fatty acid synthesis. Inhibited by leptin.

Adiponectin

adiposity signal, may be orexigenic or anorexigenic. Regulates basal metabolic rate and increases insulin sensitivity and fatty acid oxidation. Levels are reduced in obesity and anorexia. Not well understood.

Incretins

anorexigenic gut hormones including GLP-1 and GIP, increases insulin secretion, inhibits glucagon and gastric acid secretion, decreases gastric emptying and decreases appetite.

Pancreatic Polypeptide

anorexigenic, expressed in the distal GI and does not cross the BBB. Increases in proportion to caloric intake, ghrelin, motilin and gastric distention.

Protein Tyrosine Tyrosine (PYY)

anorexigenic, secreted in the ileum and colon, high fat foods lead to increased PYY. It increases POMC and decreases NPY.

POMC/ CART neurons

are anorexigenic neurons found in the arcuate nuclei and produce alpha MSH which stimulates the MCR-4 receptors on the paraventricular nuclei leading to decreased food intake and increased energy expenditure.

Orexin expressing neurons

are found in the lateral and posterior parts of the hypothalamus and project throughout the brain. Believed to play a role in emotional and motivational feeding behavior. They also increase wakefulness and suppress REM sleep.

AgRP/NPY neurons

are orexigenic neurons foundi n the arcuate nuclei, they produce agouti related peptide and neuropeptide Y in response to decreased energy stores. These inhibit the paraventricular nucleus and lead to increased appetite.

Paraventricular nuclei

decreases eating, lesions lead to excessive eating

Oxyntomodulin

glucagon derived gut peptide, anorexigenic, suppresses ghrelin effects in the brain.

Dorsomedial nuclei

increases eating, lesions lead to decreased eating

Leptin

long-term, anorexigenic adiposity signal secreted in proportion to adipose stores, promotes MSH synthesis to suppress hunger and reduces effects of NPY on POMC receptors. Important in regulating overall body weight. The body adapts to leptin by minimizing energy usage. Leptin replacement therapy considered as a treatment for obesity in leptin- deficient patients.

Insulin (hunger and satiety)

long-term, anorexigenic adiposity signal, inhibits AgRP and stimulates POMC/CART

Cortisol (hunger and satiety)

orexigenic

Ghrelin

orexigenic signal secreted by the stomach, small intestine and colon; increases secretion of growth hormone and stimulates NPY and AgRP causing GABA release which inhibits POMC nuclei.

Galanin

orexigenic, expressed in the gut and the brain, it binds GALR1 in the hypothalamus. Results in increased food intake, the effect is much smaller and shorter lived than NPY.