p75 Neurotrophin Receptor Regulates Energy Balance in Obesity

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

doi:10.1016/j.celrep.2015.12.028

Cell Reports (Jan 2016)

p75 Neurotrophin Receptor Regulates Energy Balance in Obesity

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

Affiliations

Bernat Baeza-Raja: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA
Benjamin D. Sachs: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
Pingping Li: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Frank Christian: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK
Eirini Vagena: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA
Dimitrios Davalos: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA
Natacha Le Moan: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA
Jae Kyu Ryu: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA
Shoana L. Sikorski: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
Justin P. Chan: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA
Miriam Scadeng: Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA
Susan S. Taylor: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
Miles D. Houslay: Institute of Pharmaceutical Science, King’s College London, London SE1 9NH, UK
George S. Baillie: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK
Alan R. Saltiel: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Jerrold M. Olefsky: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Katerina Akassoglou: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA

DOI: https://doi.org/10.1016/j.celrep.2015.12.028
Journal volume & issue: Vol. 14, no. 2
pp. 255 – 268

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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