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Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons

2009; Cell Press; Volume: 9; Issue: 6 Linguagem: Inglês

10.1016/j.cmet.2009.05.003

1932-7420

Lihong Huo, Kevin Gamber, Sarah Greeley, J. Fernando Silva, Nicholas Huntoon, Xing-Hong Leng, Christian Bjørbæk,

Adipose Tissue and Metabolism

Summary Leptin plays a pivotal role in regulation of energy balance. Via unknown central pathways, leptin also affects peripheral glucose homeostasis and locomotor activity. We hypothesized that, specifically, pro-opiomelanocortin (POMC) neurons mediate those actions. To examine this possibility, we applied Cre-Lox technology to express leptin receptors (ObRb) exclusively in POMC neurons of the morbidly obese, profoundly diabetic, and severely hypoactive leptin receptor-deficient Lepr db/db mice. Here, we show that expression of ObRb only in POMC neurons leads to a marked decrease in energy intake and a modest reduction in body weight in Lepr db/db mice. Remarkably, blood glucose levels are entirely normalized. This normalization occurs independently of changes in food intake and body weight. In addition, physical activity is greatly increased despite profound obesity. Our results suggest that leptin signaling exclusively in POMC neurons is sufficient to stimulate locomotion and prevent diabetes in the severely hypoactive and hyperglycemic obese Lepr db/db mice.