Leptin action via hypothalamic nitric oxide synthase-1 neurons controls energy balance

• Published in: Nature medicine Vol. 18; no. 5; pp. 820 - 823
• Main Authors: Leshan, Rebecca L., Greenwald-Yarnell, Megan, Patterson, Christa M., Gonzalez, Ian E., Myers, Martin G.
• Format: Journal Article
• Language: English
• Published: 01-05-2012
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.2724

Few effective measures exist to combat the worldwide obesity epidemic
1
, and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte hormone that signals the status of cellular energy stores, acts via multiple types of leptin receptor (LepR-b)-expressing neurons in the brain to control feeding, energy expenditure and endocrine function
2
–
4
. The modest contributions to energy balance attributable to leptin action via many previously-studied LepR-b populations
5
–
9
suggest that other, heretofore unidentified, hypothalamic LepR-b neurons play important roles. Here, we examine the role of LepR-b in neuronal nitric oxide synthase (NOS1)-expressing (LepR-b
NOS1
) neurons that comprise approximately 20% of hypothalamic LepR-b neurons.
Nos1
cre
-mediated ablation of LepR-b (
Lepr
NOS1KO
mice) produces hyperphagic obesity, decreased energy expenditure and hyperglycemia approaching that of LepR-b-null mice. In contrast, endocrine functions in
Lepr
NOS1KO
mice are relatively spared. Thus, hypothalamic LepR-b
NOS1
neurons are essential for the control of energy balance by leptin.