Appetite and Satiety

Question 1

What are the mechanisms of regulating satiety?

Answer 1

• Satiety is the suppression of appetite after a meal.
• Food in the gut causes the release of CCK, PYY and GLP-1 which induce satiety.
• Longer term cues from leptin (fat stores) act to produce long term suppression of appetite.

Question 2

Describe the different hormones which regulate satiety.

Answer 2

1. Cholecystokinin (CCK): A large 58 AA peptide hormone which is synthesised in the intestinal epithelial cells and released into the duodenum.
   - Causes reduced food intake making the individual less hungry and higher concentrations
2. Polypeptide YY (PYY): A 36 AA peptide hormone produced in intestinal cells then released into the ilium. It binds to receptors in the gut and brain.
   - PYY3-36 which is the form in humans suppresses appetite unlike its rat counter part PYY1-36.
   - Also reduced pre-meal ghrelin.
3. Glucagon-like peptide 1 (GLP-1): Reduces food intake and the rate of hunger while increasing fullness.
   - Product of pro-glucagon gene and is released from L cells, inhibits gastric emptying.
4. Oxyntomodulin (OXM): Also released from L cells in addition to oxyntic cells. From the pre-glucagon gene.
5. Obestatin: Peptide produced from the gene that encodes ghrelin, released from cells lining the small intestine.

Question 3

What are adiposity signals?

Answer 3

• The two hormones which exist to inform the brain about levels of fat stores in the body. They are insulin (pancreatic beta cells) and leptin (white adipose tissue in small intestine).
  1. Leptin (cytokine family) : 146 AA long which binds to Ob-Rb leptin receptors located on the hypothalamic neuron in the arcuate nucleus.
• Intracerebroventricular (ICV) leptin inhibits food intake and reduce body weight of rodent models.
• Neuron specific deletion of this Ob-Rb receptor leads to obesity.
  2. Insulin: Receptors also present in high levels in ARC, it has the ability to inhibit food intake as well as deletion of any receptors leading to obesity.

Question 4

Specify the peptides and hormones involved in hypothalamic control of metabolism.

Answer 4

1. Neuropeptide Y (NPY): - A 36 AA long peptide as well as one of the most abundant in the cell.
   - Stimulates food intake and reduces energy expenditure.
   - Repeated administration causes obesity therefore an antagonist of the receptors would be needed.
2. Alpha-Melanocyte Stimulating Hormone (MSH): A non-opioid peptide encoded by POMC gene.
   - The expression of POMC is reduced during periods of fasting or increased satiation.
   - Binds to MC-4 causing an inhibition of food intake.
   - Agouti is an antagonist of MC-4 which leads to obesity.
3. Agouti-related protein: Co-expressed with NPY in ARC and causes long lasting increases to food intake.