Medium-chain fatty acids enhance expression and histone acetylation of genes related to lipid metabolism in insulin-resistant adipocytes

Abstract

Background The expressions of genes related to lipid metabolism are decreased in adipocytes with insulin resistance. In this study, we examined the effects of fatty acids on the reduced expressions and histone acetylation of lipid metabolism-related genes in 3T3-L1 adipocytes treated with insulin resistance induced by tumor necrosis factor (TNF)-α. Methods Short-, medium-, and long-chain fatty acid were co-administered with TNF-α in 3T3-L1 adipocytes. Then, mRNA expressions and histone acetylation of genes involved in lipid metabolism were determined using mRNA microarrays, qRT-PCR, and chromatin immunoprecipitation assays. Results We found in microarray and subsequent qRT-PCR analyses that the expression levels of several lipid metabolism-related genes, including Gpd1 , Cidec , and Cyp4b1 , were reduced by TNF-α treatment and restored by co-treatment with a short-chain fatty acid (C4: butyric acid) and medium-chain fatty acids (C8: caprylic acid and C10: capric acid). The pathway analysis of the microarray showed that capric acid enhanced mRNA levels of genes in the PPAR signaling pathway and adipogenesis genes in the TNF-α-treated adipocytes. Histone acetylation around Cidec and Gpd1 genes were also reduced by TNF-α treatment and recovered by co-administration with short- and medium-chain fatty acids. General significance Medium- and short-chain fatty acids induce the expressions of Cidec and Gpd1 , which are lipid metabolism-related genes in insulin-resistant adipocytes, by promoting histone acetylation around these genes.

Dietary Supplementation of Inulin Contributes to the Prevention of Estrogen Receptor-Negative Mammary Cancer by Alteration of Gut Microbial Communities and Epigenetic Regulations

“…Isobutyrate, valerate, and isovalerate, as well as medium-chain fatty acids caproic acid (caproic acid level was undetectable due to lower than the Limit of Quantitation), isocaproic acid, and octanoic acid were also analyzed. Medium chain fatty acids were found to promote histone acetylation to restore the metabolism-related genes [51]. The epigenetic regulating characteristics of SCFAs and increased plasma propionic acid level by inulin treatment led to the hypothesis that propionate can potentially induce epigenetic changes in the mammary tumor site in mice.…”