Sodium butyrate remodels whole genome nucleosome maps and attenuates high fat diet‐induced mitochondrial dysfunction in skeletal muscle from C57BL6/J mice (1072.1)

Abstract

High fat diets (HFDs) largely contribute to the onset and progression of obesity and type 2 diabetes and are used to generate models of diet‐induced obesity and insulin resistance; yet, the epigenetic mechanisms underlying the effects of HFDs are not fully understood. Here, we determined whole genome differences in nucleosome occupancy or positioning in skeletal muscle from C57BL6/J mice fed either a 10% low fat diet (LFD), 60% HFD or 60% HFD plus sodium butyrate (NaB) for 9wks using microccocal nuclease digestion followed by high throughput sequencing (MNase‐seq). Additionally, metabolomics of 45 various acylcarnitine species and ratios and immunohistochemistry for fiber typing were performed in the quadriceps muscle. We show that NaB supplementation prevents HFD‐induced obesity and insulin resistance and that diet‐induced changes in nucleosome occupancy and positioning are associated with parallel increases in muscle mitochondrial function and type 1 oxidative fiber content. Targeted analysis of peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (Pgc1α), also suggests that ‐1 nucleosome positioning within the Pgc1α promoter may be important in diet‐induced mitochondrial adaptation. These data provide additional identified genomic loci that may be epigenetically regulated by diet to determine skeletal muscle mitochondrial adaptation.Grant Funding Source: Supported by NIH NIDDK 5T32‐DK064584‐09 (TMH), NIH COBRE 8P20‐GM103528‐07 and NORC 5P30‐DK072476‐07