L9 & 10 Obesity

Question 0

What are the key hypothalamic hormone regulated by leptin?

Answer 0

• orexigenic (stimulate appetite): Neuropeptide Y; agouti-related peptide (AgRP)
  = leptin can reduce these hormones so reduce feeding
• anorexigenic (reduce appetite): melanocyte stimulating hormone (alpha MSH) ; cocaine and amphetamine-related transcript
  = leptin can increase these hormones so increase feeding

Question 1

What is leptin?

Answer 1

• a polypeptide hormone that is secreted by adipose tissues
• has a positive correlation with adipose tissues, ie higher = more leptin released
• leptin is a sign indicating the fed state

Question 2

Is there a single gene which causes obesity?

Answer 2

• NO. it is not a monogenic disorder and very rare (can have a frameshift in leptin or MC4R, which leptin binds to)
• mostly polygenic, e.g. Bardet-Biedl syndrome and Prader-Willi syndrome associate with voracious appetite

Question 3

What are the two more well known genes which have been identified for causing obesity?

Answer 3

• MC4R and FTO gene

* FTO is the fused toe gene (babies who have fused toes)

Question 4

What other problems with adults who have leptin deficiency?

Answer 4

• infertility. FSH/LH/oestrodiol/testosterone all at pre-pubertal levels)

Question 5

What are the other satiety inducing peptides other than leptin? Where are they produced?

Answer 5

• Glucagon-like peptide 1; PYY; Cholecystokinin

- they are produced in L cells in small intestine

Question 6

What are the hunger-inducing peptides?

Answer 6

• Ghrelin -> produced in X/A cells in stomach and acts centrally oon receptors in arcuate nucleus and ventromedial hypothalamus
• orexins A and B

Question 7

What are the surgical options for severe obesity?

Answer 7

• Roux-en-Y: by pass the stomach and proximal small intestine. Reconnect with distal intestine so reduce ghrelin (secrete by stomach) and increases GLP-1 (= satiety hormone. secrete by L cells in small intestine)
• Sleeve gastrectomy: remove part of stomach only and reconnect with proximal small intestine

Question 8

What are the potential therapies for obesity?

Answer 8

• mitochondrial uncoupling protein activators: where protons are leak instead of generating ATP in oxidative phosphorylation. Heat is released instead and burn off excess energy
• side effects: DEATH!

Question 9

What can adipose tissues release?

Answer 9

1) adiponectin: increase insulin sensitivity in muscle/ liver
2) leptin: decrease appetite
3) TNF alpha: reduce insulin sensitivity in muscle/ fat
4) resistin: decrease insulin sensitivity in liver