p75 neurotrophin receptor regulates energy balance in obesity

Baeza-Raja, B. et al. (2016) p75 neurotrophin receptor regulates energy balance in obesity. Cell Reports, 14(2), pp. 255-268. (doi: 10.1016/j.celrep.2015.12.028) (PMID:26748707) (PMCID:PMC4831919)

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Obesity and metabolic syndrome reflect the dysregulation of molecular pathways that control energy homeostasis. Here, we show that the p75 neurotrophin receptor (p75NTR) controls energy expenditure in obese mice on a high-fat diet (HFD). Despite no changes in food intake, p75NTR-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. p75NTR 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 p75NTR or transplantation of p75NTR-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 p75NTR 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Baillie, Professor George
Authors: Baeza-Raja, B., Sachs, B. D., Li, P., Christian, F., Vagena, E., Davalos, D., Le Moan, N., Ryu, J. K., Sikorski, S. L., Chan, J. P., Scadeng, M., Taylor, S. S., Houslay, M. D., Baillie, G. S., Saltiel, A. R., Olefsky, J. M., and Akassoglou, K.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cell Reports
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Cell Reports 14(2):255-268
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438301Phosphodiesterase-4 isoforms - intracellular targeting, regulation and potential therapeutic targetsMiles HouslayMedical Research Council (MRC)G0600765RI NEUROSCIENCE & PSYCHOLOGY
588611cAMP phosphodiesterase-4: signalling complexes, regulation and potential therapeutic targets.George BaillieMedical Research Council (MRC)MR/J007412/1RI CARDIOVASCULAR & MEDICAL SCIENCES