Activation of atypical protein kinase C zeta toward TC10 is regulated by high-fat diet and aerobic exercise in skeletal muscle

作者：Saito Misato; Lessard S J; Rivas Donato A; Reeder Donald W; Hawley John A; Yaspelkis Ben B III^*

来源：Metabolism-Clinical and Experimental, 2008, 57(9): 1173-1180.

DOI：10.1016/j.metabol.2008.03.023

We determined whether Sustained aerobic exercise reverses high-fat diet-induced impairments in the c-Cbl associated protein (CAP)/ Casitas b-lineage lymphoma (c-Cbl) signaling cascade in rodent skeletal muscle. Sprague-Dawley rats were placed into either control (n = 16) or high-fat-fed (n = 32) diet groups for 4 weeks. During a Subsequent 4-week experimental period, 16 high-fat-fed rats remained sedentary, 16 high-fat-fed rats completed 4 weeks of exercise training, and control animals were sedentary and remained on the control diet. After the intervention period, animals were subjected to hind limb perfusions in the presence (n = 8 per group) or absence (n = 8 per group) of insulin. In the plasma membrane fractions, neither high-fat feeding nor exercise training altered adaptor protein with PH and SH2 domains, (APS), c-Cbl, or TC10 protein concentrations. In contrast, CAP protein concentration and insulin-stimulated plasma membrane c-Cbl tyrosine phosphorylation were reduced by high-fat feeding; but exercise training reversed these impairments. Of note was that insulin-stimulated atypical protein kinase C kinase activity toward TC10 was reduced by high-fat feeding but normalized by exercise training. We conclude that sustained (4 weeks) exercise training can reverse high-fat diet-induced impairments on the CAP/c-Cbl pathway in high-fat-fed rodent skeletal muscle. We also provide the first evidence that the CAP/c-Cbl insulin signaling cascade in skeletal muscle may directly interact with components of the classic (phosphoinositide 3-kinase dependent) insulin signaling cascade.

• 出版日期2008-9