4.7 Article

Perilipin 1 binds to aquaporin 7 in human adipocytes and controls its mobility via protein kinase A mediated phosphorylation

Journal

METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 65, Issue 12, Pages 1731-1742

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2016.09.004

Keywords

Aquaporin 7; Perilipin 1; Adipocyte; Glycerol; PKA

Funding

  1. Swedish Research Council [2011-2891]
  2. Cancer Foundation [2010/1171, 2014/575]
  3. Novo Nordisk Foundation [9807]
  4. Olle Engkvist Byggmastare foundation
  5. AFA forsakring and Diabetesfonden [DIA2015-035]
  6. Novo Nordisk Fonden [NNF15OC0015906, NNF14OC0009807] Funding Source: researchfish

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Accumulating evidence suggests that dysregulated glycerol metabolism contributes to the pathophysiology of obesity and type 2 diabetes. Glycerol efflux from adipocytes is regulated by the aquaglyceroporin AQP7, which is translocated upon hormone stimulation. Here, we propose a molecular mechanism where the AQP7 mobility in adipocytes is dependent on perilipin 1 and protein kinase A. Biochemical analyses combined with ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation. Together, these findings are indicative of how glycerol release is controlled in adipocytes, and may pave the way for the future design of drugs against human metabolic pathologies. (C) 2016 The Authors. Published by Elsevier Inc.

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