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- Title
Fyn Kinase Deficiency Increases Peripheral Tissue Insulin Sensitivity by Improving Fatty Acid Oxidation and Lipolysis.
- Authors
Bastie, Claire C.; Zong, Hai-Hong; Xu, Jun; Judex, Stefan; Kurland, Irwin J.; Pessin, Jeffrey E.
- Abstract
The Src family of non-receptor tyrosine kinases is composed of nine members that share a conserved structure. Among them, Fyn has been implicated in the regulation of insulin action (i.e, association with IRS and c-Cb1 proteins). Fyn has also been shown to be responsible for adipocyte insulin-stimulated caveolin tyrosine phosphorylation. Moreover, pharmacological inhibition of Src family kinase activity inhibits adipogenesis of 3T3L1 preadipocytes. Despite the apparent relationship between insulin signaling and Fyn function in culture adipocytes, the in vivo role of Fyn in the metabolic regulation has not been studied. To address this issue, we have investigated the metabolic phenotype of the Fyn null mice. We found that the Fyn null mice displayed a reduced body weight with a marked decrease in adiposity resulting from a decrease of adipocyte cell size. These mice had a reduction in plasma fasting glucose, insulin, triglycerides and free fatty acids associated with decreased intra-hepatocellular and intra-myocellular lipid accumulation. Importantly, the Fyn null mice exhibited improved glucose tolerance resulting from increased peripheral tissue (adipose and skeletal muscle) insulin sensitivity. Moreover, whole body, adipose and skeletal muscle fatty acid uptake and oxidation were increased in the fasted but not in the fed state. This occurred concomitant with enhanced activation of AMPkinase and subsequent acetyl-CoA carboxylase inhibition. In addition, isoproterenol-induced lipolysis was drastically increased in vivo (whole animal) and in vitro (primary adipocytes). This was paralleled with an increase of HSL and perilipin phosphorylation levels in the adipose tissue of the Fyn null mice. Interestingly, in presence of insulin the lipolysis was not suppressed in the Fyn null adipocytes. Together, these data demonstrate a novel crosstalk between the Src kinase Fyn, fatty acid metabolism and improvement Of peripheral tissue insulin sensitivity due to marked improvement of fuel switching from carbohydrates to fatty acids.
- Publication
Diabetes, 2007, Vol 56, pA60
- ISSN
0012-1797
- Publication type
Academic Journal