Serotonin is an important brain chemical, or neurotransmitter, that is well-studied for its effects on mood, emotion, sleep, and energy regulation. Serotonin activity in the brain is known to exert anti-diabetic effects by maintaining blood glucose levels, but until now, it was unclear which brain cells (neurons) regulate these effects. Dr. Joel Elmquist and colleagues at the Taskforce for Obesity Research at Southwestern (TORS) Consortium, one of nine interdisciplinary research consortia funded by the Common Fund, have recently identified the group of neurons that mediate the anti-diabetic actions of serotonin. In the December 2010 issue of Nature Neuroscience, Dr. Elmquist and colleagues demonstrate that serotonin signaling in POMC neurons of the hypothalamic region of the brain regulates glucose homeostasis and insulin sensitivity. To study the effects of serotonin signaling in POMC neurons, researchers compared two groups of genetically engineered mice. In one group of mice, serotonin signaling was eliminated in every cell in the body. In the second group of mice, serotonin signaling was eliminated in every cell except for POMC neurons. When comparing these two groups of mice, researchers discovered that mice with no serotonin signaling anywhere developed metabolic problems such as insulin resistance in the liver, while mice with serotonin signaling in POMC neurons alone did not have these metabolic problems. These results point to POMC neurons as a critical mediator of serotonin’s anti-diabetic actions. A better understanding of how blood glucose homeostasis and insulin sensitivity are regulated by serotonin may offer insights into how to prevent the metabolic imbalances sometimes seen in patients who are taking anti-depressant or anti-psychotic drugs that affect serotonin levels.

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REFERENCES

Xu Y, Berglund ED, Sohn JW, Holland WL, Chuang JC, Fukuda M, Rossi J, Williams KW, Jones JE, Zigman JM, Lowell BB, Scherer PE, Elmquist JK. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver. Nat Neurosci 2010 Dec; 13(12): 1457-9. PMID: 21037584.