Leptin-dependent control of glucose balance and locomotor activity by POMC neurons.

Abstract

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.

• Authors: Lihong Huo, Kevin Gamber, Sarah Greeley, Jose Silva, Nicholas Huntoon, Xing-Hong Leng, Christian Bjørbaek
• Journal: Cell metabolism (Cell Metab) Vol. 9 Issue 6 Pg. 537-47 (Jun 2009) ISSN: 1932-7420 [Electronic] United States
• PMID: 19490908 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Leptin
• Receptors, Leptin
• Pro-Opiomelanocortin

Topics

• Animals
• Blood Glucose (metabolism)
• Body Weight
• Eating
• Leptin (metabolism)
• Mice
• Mice, Knockout
• Motor Activity
• Neurons (metabolism)
• Pro-Opiomelanocortin (metabolism)
• Receptors, Leptin (metabolism)
• Signal Transduction