title: High-fat feeding effects on components of the CAP/Cbl signaling cascade in Sprague-Dawley rat skeletal muscle.
abstract: The aim of this investigation was to determine whether the CAP (Cbl-associated protein)/Cbl signaling cascade is present and responsive to insulin in skeletal muscle and if high-fat feeding impairs insulin-stimulated activation of this signaling cascade. Sprague-Dawley rats were assigned to either control (n = 16) or high fat-fed (n = 16) dietary groups. After a 12-week dietary period, animals were subjected to hind limb perfusions in the presence (n = 8 per group) or absence (n = 8 per group) of insulin. High-fat feeding reduced rates of insulin-stimulated skeletal muscle phosphatidylinositol 3-kinase activity and 3-O-methylglucose transport. In plasma membrane fractions, neither the high-fat diet nor insulin altered the insulin receptor beta subunit (IR-beta), APS (adaptor protein containing PH and SH2 domains), c-Cbl, or TC10 protein concentration, but high-fat feeding did decrease CAP protein concentration. APS, c-Cbl, CAP, and TC10 messenger RNA were present in the skeletal muscle and reflected the protein concentration of experimental groups. Despite insulin-stimulated plasma membrane IR-beta tyrosine phosphorylation being unaffected by high-fat feeding, c-Cbl tyrosine phosphorylation, the kinase activity of IR-beta toward APS, and glucose transporter 4 protein concentration were all significantly reduced in insulin-stimulated plasma membrane prepared from the skeletal muscle of high fat-fed animals. These findings suggest that the CAP/Cbl signaling cascade is present in skeletal muscle, activated by insulin, and impaired by high-fat feeding.
authors.affiliation: Department of Kinesiology, College of Health and Human Development, California State University Northridge, Northridge, CA 91330-8287, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bernard
authors.forename: Donald W
authors.initials: DW
authors.lastname: Reeder
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Herr
authors.forename: Donato A
authors.initials: DA
authors.lastname: Rivas
authors.forename: Ben B
authors.initials: BB
authors.lastname: Yaspelkis
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000502:physiology; D007328:Insulin / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000502:physiology*; D052097:Quadriceps Muscle / Q000502:physiology*; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D004041:Dietary Fats; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D012313:RNA; D050721:Proto-Oncogene Proteins c-cbl; D019869:Phosphatidylinositol 3-Kinases; C503256:RHOQ protein, human; D020741:rho GTP-Binding Proteins