title: Chronic high fat feeding attenuates load-induced hypertrophy in mice.
abstract: The incidence of obesity and obesity-related conditions, such as metabolic syndrome and insulin resistance, is on the increase. The effect of obesity on skeletal muscle function, especially the regulation of muscle mass, is poorly understood. In this study we investigated the effect of diet-induced obesity on the ability of skeletal muscle to respond to an imposed growth stimulus, such as increased load. Male C57BL/6 mice were randomized into two diet groups: a low fat, high carbohydrate diet (LFD) and a high fat, low carbohydrate diet (HFD) fed ad libitum for 14 weeks. Mice from each diet group were divided into two treatment groups: sedentary control or bilateral functional overload (FO) of the plantaris muscle. Mice were evaluated at 3, 7, 14 or 30 days following FO. By 14 days of FO, there was a 10% reduction (P < 0.05) in absolute growth of the plantaris in response to overload in HFD mice vs. LFD mice. By 30 days the attenuation in growth increased to 16% in HFD mice compared to LFD mice. Following FO, there was a reduction in the formation of polysomes in the HFD mice relative to the LFD mice, suggesting a decrease in protein translation. Further, activation of Akt and S6K1, in response to increased mechanical loading, was significantly attenuated in the HFD mice relative to the LFD mice. In conclusion, chronic high fat feeding impairs the ability of skeletal muscle to hypertrophy in response to increased mechanical load. This failure coincided with a failure to activate key members of the Akt/mTOR signalling pathway and increase protein translation.
authors.affiliation: Department of Neurobiology, Physiology and Behavior, 196 Briggs Hall, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Sitnick
authors.forename: Sue C
authors.initials: SC
authors.lastname: Bodine
authors.forename: John C
authors.initials: JC
authors.lastname: Rutledge
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001823:Body Composition / Q000502:physiology; D002499:Centrifugation, Density Gradient; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development*; D009765:Obesity / Q000503:physiopathology*; D051058:Oncogene Protein v-akt / Q000502:physiology; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases
chemical_list: D004041:Dietary Fats; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C546843:mTOR protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3