Increased PDK4 expression via PGC‐1α/ERRα – dependent mechanism in mouse skeletal muscle after high fat feeding

Abstract

The key regulator of cellular energy metabolism is the peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α). It is shown that PGC‐1α coactivates the pyruvate dehydrogenase kinase (PDK4) gene expression via the estrogen related receptor (ERRα). Our aim was to investigate the effects of high fat (HF) feeding and physical activity in the expression levels of these genes in the skeletal muscles of C57BL/6J mice.The HF animals showed an altered blood lipid profile suggesting changes in the overall lipid metabolism. The expression level of PGC‐1α was slightly down‐regulated after HF feeding, although voluntary wheel running restored the levels. Upregulation of ERRα and PDK4 was seen after HF diet and this combined with running had even more profound effects on the expression levels.Although HF diet did not increase the PGC‐1α mRNA levels, we hypothesize that the regulation of energy metabolism after HF feeding leads to a situation where PDK4 inhibits the glucose oxidation coincident with the increased mitochondrial fatty acid oxidation. Whether the fatty acid oxidation is reduced de facto after HF feeding, as the hypothesis on accumulation of ectopic lipids might suggest, remains to be further clarified. The research was funded by the Finnish Ministry of Education.