Ectopic intramuscular lipid accumulation is considered to promote insulin resistance. Skeletal muscle peroxisomes have potential to combat lipid-induced insulin resistance as they provide an alternative route for lipid disposal that can alleviate the cellular and mitochondrial lipid burden. Both Pgc1α and high fat diets (HFD) have been reported to increase peroxisomes in skeletal muscle. In this study, we hypothesized induction of peroxisomes in response to a HFD would require Pgc1α.


To test this hypothesis we fed Pgc1α-deficient mice and C57BL/6J control mice a 60% HFD for 12 weeks and results were compared to cohorts fed a low-fat (10%) matched control diet. Adaptations in peroxisomal and mitochondrial lipid metabolism were tested.


The HFD increased body weight, fat mass, and lean mass similarly in both genotypes (p< 0.05). Pgc1α expression was slightly increased in C57BL/6J mice fed the HFD, whereas this was naturally negated in Pgc1α-deficient mice. Pgc1α KO mice exhibited lower baseline complete (CO2) and incomplete (acid soluble metabolites; ASM) palmitate oxidation than C57BL/6J mice, suggesting reduced baseline mitochondrial fat oxidation. Interestingly, in response to the HFD, palmitate oxidation increased in C57BL/6J mice; however, this was negated in Pgc1α-deficient mice. Alternatively, Pgc1α deficiency had no effect on peroxisomal gene expression and fatty acid oxidation [measured by lignocerate (C24:0) oxidation] in the basal state and did not alter the observed HFD-induced increase in peroxisomal adaptations.


Overall, results herein suggest Pgc1α is required for upregulation of mitochondrial fatty acid oxidation pathways in response to a HFD; however, HFD-induced adaptations in peroxisomal lipid metabolism occur independent of Pgc1α.