Leptin regulation of bone mass, appetite and energy expenditure relies on its ability to inhibit serotonin synthesis in the brainstem

By Vijay K. Yadav, Franck Oury, N. Suda, Zhong-Wu Liu, Xiao-Bing Gao, C. Confavreux, K. C. Klemenhagen, Kenji F. Tanaka, Jay A. Gingrich, X. Edward Guo and 5 more. Cell, 2009

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Leptin inhibition of bone mass accrual requires the integrity of specific hypothalamic neurons but not expression of its receptor on these neurons. The same is true for its regulation of appetite and energy expenditure. This suggests that leptin acts elsewhere in the brain to achieve these three functions. We show here that brainstem-derived serotonin (BDS) favors bone mass accrual following its binding to Htr2c receptors on ventromedial hypothalamic neurons and appetite via Htr1a and 2b receptors on arcuate neurons. Leptin inhibits these functions and increases energy expenditure because it reduces serotonin synthesis and firing of serotonergic neurons. Accordingly, while abrogating BDS synthesis corrects the bone, appetite and energy expenditure phenotypes caused by leptin deficiency, inactivation of the leptin receptor in serotonergic neurons recapitulates them fully. This study modifies the map of leptin signaling in the brain and identifies a molecular basis for the common regulation of bone and energy metabolisms.

Subfields: Endocrine and Autonomic Systems, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/617fa39a074acb0528476cd0d55b79b91bb139d5

Citations in the corpus

• Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons (2011, neutral): “, 2008), and possibly serotonin neurons in the raphe (Yadav et al., 2009).”