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p75 Neurotrophin Receptor Regulates Energy Balance in Obesity.
Baeza-Raja, Bernat; Sachs, Benjamin D; Li, Pingping; Christian, Frank; Vagena, Eirini; Davalos, Dimitrios; Le Moan, Natacha; Ryu, Jae Kyu; Sikorski, Shoana L; Chan, Justin P; Scadeng, Miriam; Taylor, Susan S; Houslay, Miles D; Baillie, George S; Saltiel, Alan R; Olefsky, Jerrold M; Akassoglou, Katerina.
Afiliación
  • Baeza-Raja B; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Sachs BD; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Li P; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Christian F; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
  • Vagena E; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Davalos D; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Le Moan N; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Ryu JK; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Sikorski SL; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Chan JP; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Scadeng M; Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Taylor SS; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
  • Houslay MD; Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK.
  • Baillie GS; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
  • Saltiel AR; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Olefsky JM; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Akassoglou K; Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: kakassoglou@gladstone.ucsf.edu.
Cell Rep ; 14(2): 255-68, 2016 Jan 12.
Article en En | MEDLINE | ID: mdl-26748707
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptor de Factor de Crecimiento Nervioso / Metabolismo de los Lípidos / Obesidad Límite: Animals Idioma: En Revista: Cell Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptor de Factor de Crecimiento Nervioso / Metabolismo de los Lípidos / Obesidad Límite: Animals Idioma: En Revista: Cell Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos