Activation of atypical protein kinase Czeta toward TC10 is regulated by high-fat diet and aerobic exercise in skeletal muscle
Saito, Misato Lessard, S. J. Rivas, Donato A. Reeder, Donald W. Hawley, John Alan Yaspelkis, Ben B.
Saito, Misato
Lessard, S. J.
Rivas, Donato A.
Reeder, Donald W.
Hawley, John Alan
Yaspelkis, Ben B.
Abstract
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 Cζ 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.
Keywords
Date
2008
Type
Journal article
Journal
Metabolism: Clinical and experimental
Book
Volume
57
Issue
9
Page Range
1173-1180
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences