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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Abstract

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
Status:Published
Refereed:Yes
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 > Institute of Cardiovascular and Medical Sciences
Journal Name:Cell Reports
Publisher:Elsevier
ISSN:2211-1247
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