Integrative Metabolic Regulation of Peripheral Tissue Fatty Acid Oxidation by the Src Kinase Family Member Fyn

Claire C. Bastie, Haihong Zong, Jun Xu, Bhavin Busa, Stefan Judex, Irwin J. Kurland, Jeffrey E E. Pessin

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Mice null for Fyn (a member of the Src family of nonreceptor tyrosine kinases) display a reduced percentage of adipose mass associated with decreased adipocyte cell size. In parallel, there is a substantial reduction in fasting plasma glucose, insulin, triglycerides, and free fatty acids concomitant with decreased intrahepatocellular and intramyocellular lipid accumulation. Importantly, the Fyn null mice exhibit improved glucose tolerance resulting from increased peripheral tissue (adipose and skeletal muscle) insulin sensitivity with a very small effect in the liver. Moreover, whole-body, adipose, and skeletal muscle fatty acid uptake and oxidation are increased along with AMP kinase activation and acetyl-CoA carboxylase inhibition. Together, these data demonstrate crosstalk between Src-family kinase activity and fatty acid oxidation and show that the loss of Fyn markedly improves peripheral tissue insulin sensitivity by relieving a selective negative modulation of AMP kinase activity in adipose tissue and skeletal muscle.

Original languageEnglish (US)
Pages (from-to)371-381
Number of pages11
JournalCell metabolism
Volume5
Issue number5
DOIs
StatePublished - May 9 2007
Externally publishedYes

Keywords

  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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