Specifically, in our review, we first separately investigate the epigenetic regulation mediated by KBs and SIRT1, respectively, and then how these epigenetic modifications may act in the fine-tuning of adipose tissue remodeling, in the evolution of nonalcoholic fatty liver disease and in the resolution of low-grade systemic inflammation, a common aspect of all metabolic diseases. This evidence concerns the gene SIRT1 and metabolic disease.