| First Author | Peck B | Year | 2018 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 314 |
| Issue | 3 | Pages | R468-R477 |
| PubMed ID | 29187383 | Mgi Jnum | J:260321 |
| Mgi Id | MGI:6148186 | Doi | 10.1152/ajpregu.00521.2016 |
| Citation | Peck B, et al. (2018) Mice lacking PKC-theta in skeletal muscle have reduced intramyocellular lipid accumulation and increased insulin responsiveness in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 314(3):R468-R477 |
| abstractText | Protein kinase C-theta (PKC-theta) is a lipid-sensitive molecule associated with lipid-induced insulin resistance in skeletal muscle. Rodent models have not cohesively supported that PKC-theta impairs insulin responsiveness in skeletal muscle. The purpose of this study was to generate mice that lack PKC-theta in skeletal muscle and determine how lipid accumulation and insulin responsiveness are affected in that tissue. Mice lacking PKC-theta in skeletal muscle (SkM(PKCthetaKO)) and controls (SkM(PKCthetaWT)) 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(PKCthetaWT) and SkM(PKCthetaKO) mice on a RD. SkM(PKCthetaKO) 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(PKCthetaWT) mice on a HFD. Intramyocellular lipid accumulation ( P < 0.0001), fatty acid binding protein 4, and TNF-alpha mRNA levels ( P < 0.05) were markedly reduced in SkM(PKCthetaKO) compared with SkM(PKCthetaWT) mice on a HFD. As a result, fasting hyperglycemia was mitigated and insulin responsiveness, as indicated by Akt phosphorylation, was maintained in SkM(PKCthetaKO) on a HFD. Liver lipid accumulation was not affected by genotype, suggesting the deletion of PKC-theta from skeletal muscle has a tissue-specific effect. PKC-theta 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. |
