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

Musashi Kawamura; Naoki Goda; Natsuyo Hariya; Mayu Kimura; Shiori Ishiyama; Takeo Kubota; Kazuki Mochizuki

doi:10.1016/j.bbrep.2021.101196

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

Biochem Biophys Rep. 2022 Jan 5:29:101196. doi: 10.1016/j.bbrep.2021.101196. eCollection 2022 Mar.

Authors

Musashi Kawamura¹, Naoki Goda², Natsuyo Hariya³, Mayu Kimura¹, Shiori Ishiyama^{4

2}, Takeo Kubota⁵, Kazuki Mochizuki^{1

2

4}

Affiliations

¹ Graduate School of Life and Environmental Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
² Faculty of Life and Environmental Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
³ Department of Nutrition, Faculty of Health and Nutrition, Yamanashi Gakuin University, 2-4-5, Sakaori, Kofu, Yamanashi, 400-8575, Japan.
⁴ Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
⁵ Department of Child Studies, Faculty of Child Studies, Seitoku University, 550, Iwase, Matsudo, Chiba, 271-8555, Japan.

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.

Keywords: Adipocyte; Histone acetylation; Insulin resistance; Medium-chain fatty acid; Short-chain fatty acid.