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Mice lacking PKC-θ in skeletal muscle have reduced intramyocellular lipid accumulation and increased insulin responsiveness in skeletal muscle

2017; American Physiological Society; Volume: 314; Issue: 3 Linguagem: Inglês

10.1152/ajpregu.00521.2016

1522-1490

Bailey D. Peck, Josh R. Huot, Tim Renzi, Susan T. Arthur, Michael J. Turner, Joseph Marino,

Diet and metabolism studies

Protein kinase C-θ (PKC-θ) is a lipid-sensitive molecule associated with lipid-induced insulin resistance in skeletal muscle. Rodent models have not cohesively supported that PKC-θ impairs insulin responsiveness in skeletal muscle. The purpose of this study was to generate mice that lack PKC-θ in skeletal muscle and determine how lipid accumulation and insulin responsiveness are affected in that tissue. Mice lacking PKC-θ in skeletal muscle (SkM PKCθKO ) and controls (SkM PKCθWT ) were placed on a regular diet (RD) or high-fat diet (HFD) for 15 wk, followed by determination of food intake, fasting glucose levels, lipid accumulation, and insulin responsiveness. There were no differences between SkM PKCθWT and SkM PKCθKO mice on a RD. SkM PKCθKO mice on a HFD gained less weight from 10 through 15 wk of dietary intervention ( P < 0.05). This was likely due to less caloric consumption ( P = 0.0183) and fewer calories from fat ( P < 0.001) compared with SkM PKCθWT mice on a HFD. Intramyocellular lipid accumulation ( P < 0.0001), fatty acid binding protein 4, and TNF-α mRNA levels ( P < 0.05) were markedly reduced in SkM PKCθKO compared with SkM PKCθWT mice on a HFD. As a result, fasting hyperglycemia was mitigated and insulin responsiveness, as indicated by Akt phosphorylation, was maintained in SkM PKCθKO on a HFD. Liver lipid accumulation was not affected by genotype, suggesting the deletion of PKC-θ from skeletal muscle has a tissue-specific effect. PKC-θ is a regulator of lipid-induced insulin resistance in skeletal muscle. However, the effects of this mutation may be tissue specific. Further work is warranted to comprehensively evaluated whole body metabolic responses in this model.