Table 1.

Examples of epigenetic modifications and microbiome-related modifications in obesity, type 2 diabetes, and NAFLD

	Obesity	Type 2 diabetes	NAFLD
Epigenetics	- H3K9me in WAT - Differently methylated obesity-related genes: HAND2, HOXC6, PPARG, SORBS2, CD36, CLDN1 - Differently methylated PPARG promoter region in omental visceral compared with subcutaneous adipose tissue	- Differently methylated genes: TCF7L2, THADA, KCNQ1, FTO, IRS1 - H3K27me3 modification of myocytes - Metformin indirectly induced hypermethylation of tumor-promoting pathway genes and inhibits cell proliferation	- Hypermethylation PNPLA3 - Differently methylated MT-DN6 gene
Microbiome	Butyrate inhibition of HDAC3 and HDAC1 reduced methylation in obesity-associated genes FTO and MC4R upon probiotic supplementation	Butyrate inhibition of HDAC differently methylated palmitate-treated human islets in genes TCF7L2, GLIS3, HNF1B, and SLC30A8	Bacterial dysbiosis leading to increased permeability, endotoxemia, and increased pro-inflammatory cytokines

H3K9me, methylation of lysine 9 on histone 3; WAT, white adipose tissue; HDAC, histone deacetylase; HDAC3, histone deacetylase 3; HDAC1, histone deacetylase 1; MT-ND6, mitochondrially encoded NADH dehydrogenase 6; H3K27me3, trimethylation of lysine 27 on histone 3; PNPLA3, patatin-like phospholipase domain containing 3