p75 Neurotrophin Receptor Regulates Energy Balance in Obesity.

Abstract

Obesity and metabolic syndrome reflect the dysregulation of molecular pathways that control energy homeostasis. Here, we show that the p75 neurotrophin receptor (p75(NTR)) controls energy expenditure in obese mice on a high-fat diet (HFD). Despite no changes in food intake, p75(NTR)-null mice were protected from HFD-induced obesity and remained lean as a result of increased energy expenditure without developing insulin resistance or liver steatosis. p75(NTR) directly interacts with the catalytic subunit of protein kinase A (PKA) and regulates cAMP signaling in adipocytes, leading to decreased lipolysis and thermogenesis. Adipocyte-specific depletion of p75(NTR) or transplantation of p75(NTR)-null white adipose tissue (WAT) into wild-type mice fed a HFD protected against weight gain and insulin resistance. Our results reveal that signaling from p75(NTR) to cAMP/PKA regulates energy balance and suggest that non-CNS neurotrophin receptor signaling could be a target for treating obesity and the metabolic syndrome.

• Authors: Bernat Baeza-Raja, Benjamin D Sachs, Pingping Li, Frank Christian, Eirini Vagena, Dimitrios Davalos, Natacha Le Moan, Jae Kyu Ryu, Shoana L Sikorski, Justin P Chan, Miriam Scadeng, Susan S Taylor, Miles D Houslay, George S Baillie, Alan R Saltiel, Jerrold M Olefsky, Katerina Akassoglou
• Journal: Cell reports (Cell Rep) Vol. 14 Issue 2 Pg. 255-68 (Jan 12 2016) ISSN: 2211-1247 [Electronic] United States
• PMID: 26748707 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Receptor, Nerve Growth Factor

Topics

• Animals
• Lipid Metabolism (physiology)
• Mice
• Mice, Knockout
• Obesity (metabolism)
• Receptor, Nerve Growth Factor (metabolism)
• Signal Transduction