Identification of Sucrose Non-Fermenting–Related Kinase (SNRK) as a Suppressor of Adipocyte Inflammation

  1. Haiyan Xu1,7
  1. 1Hallett Center for Diabetes and Endocrinology, Rhode Island Hospital, Warren Alpert
  2. Medical School of Brown University, Providence, Rhode Island
  3. 2Department of Geriatric Endocrinology, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
  4. 3Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
  5. 4Department of Molecular Pharmacology and Physiology, Brown University, Providence, Rhode Island
  6. 5Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island
  7. 6Department of Chemistry, Brown University, Providence, Rhode Island
  8. 7Pathobiology Program, Brown University, Providence, Rhode Island
  1. Corresponding author: Haiyan Xu, hxu{at}lifespan.org.

Abstract

In this study, the role of sucrose non-fermenting–related kinase (SNRK) in white adipocyte biology was investigated. SNRK is abundantly expressed in adipose tissue, and the expression level is decreased in obese mice. SNRK expression is repressed by inflammatory signals but increased by insulin sensitizer in cultured adipocytes. In vivo, adipose tissue SNRK expression can be decreased by lipid injection but enhanced by macrophage ablation. Knocking down SNRK in cultured adipocytes activates both JNK and IKKβ pathways as well as promotes lipolysis. Insulin-stimulated Akt phosphorylation and glucose uptake are impaired in SNRK knockdown adipocytes. Phosphoproteomic analysis with SNRK knockdown adipocytes revealed significantly decreased phosphorylation of 49 proteins by 25% or more, which are involved in various aspects of adipocyte function with a clear indication of attenuated mTORC1 signaling. Phosphorylation of 43 proteins is significantly increased by onefold or higher, among which several proteins are known to be involved in inflammatory pathways. The inflammatory responses in SNRK knockdown adipocytes can be partially attributable to defective mTORC1 signaling, since rapamycin treatment activates IKKβ and induces lipolysis in adipocytes. In summary, SNRK may act as a suppressor of adipocyte inflammation and its presence is necessary for maintaining normal adipocyte function.

Footnotes

  • Received August 10, 2012.
  • Accepted March 13, 2013.

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  1. Diabetes vol. 62 no. 7 2396-2409
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