Mitochondria, obesity and insulin resistance : role of SIRT3 and miRNA differentially regulated by TNFα

Obesity is associated with increased adiposity and low-grade inflammation and oxidative stress in the white adipose tissues (WAT) in which TNFa and down-regulation of Sirtuin 3 (SIRT3), a mitochondrial deacetylase, plays a major role, respectively. These conditions predispose to insulin resistance, type II diabetes (mellitus), hypertension and cardiovascular complications that are hallmarks of the metabolic syndrome. The pro-inflammatory cytokine is known to control gene expression by post-transcriptional mechanisms through the regulation of several microRNAs (miRNAs) that are short 20-22 nucleotide non-coding RNAs. The aim of our ongoing study is to identify the role of miRNAs that are differentially regulated in adipocytes stimulated with TNFα and to characterize their function in the biology of adipocytes exposed to inflammatory cytokine. The effects of TNFa and SIRT3 in the control of adipogenesis and adipocyte dedifferentiation are also analyzed.

Unraveling the roles of these regulatory miRNAs and SIRT3 might be useful in the deep understanding of the role of TNFa and the deacetylase in obesity and the associated metabolic syndrome.