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

Lihong Huo, Kevin Gamber, Sarah Greeley, Jose Silva, Nicholas Huntoon, Xing Hong Leng, Christian Bjørbæk

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


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 Leprdb/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 Leprdb/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 Leprdb/db mice.

Original languageEnglish
Pages (from-to)537-547
Number of pages11
JournalCell Metabolism
Issue number6
StatePublished - May 14 2009



ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology


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