title: 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.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Bernat
authors.initials: B
authors.lastname: Baeza-Raja
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Sachs
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Pingping
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Christian
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Eirini
authors.initials: E
authors.lastname: Vagena
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Davalos
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Le Moan
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jae Kyu
authors.initials: JK
authors.lastname: Ryu
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Shoana L
authors.initials: SL
authors.lastname: Sikorski
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Chan
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Scadeng
authors.affiliation: 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.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Taylor
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK.
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Saltiel
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
authors.affiliation: 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.
authors.forename: Katerina
authors.initials: K
authors.lastname: Akassoglou
mesh_terms: D000818:Animals; D050356:Lipid Metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020800:Receptor, Nerve Growth Factor