LAUSR

Abstract Obesity is a disease characterized by chronic inflammation and increases the risk of comorbidities such as type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular dysfunction. In obese individuals, elevated levels of plasma circulating saturated fatty acids (e.g. palmitate) contribute to subclinical chronic inflammation. Genetic variants play a major role in determining susceptibility or resistance to obesity. Some recently described variant in genetically Lean mice that leads to upregulated expression selectively in adipose tissue of the nuclear encoded mitochondrial gene thiosulfate sulfurtransferase, Tst, has been causally linked to reduced adiposity and insulin sensitisation. Here we show that macrophages derived from the high-TST expressing Lean line of mice have a reduced inflammatory response to TLR-ligand activation than those from the low-TST expressing Fat line of mice. Furthermore, using the mouse clonal 3T3-L1 adipocytes we describe a positive effect of TST upregulation via its substrates, sodium thiosulfate (STS) and the garlic compound diallyl disulfide (DADS), on palmitate-induced inflammation resulting in significant reduction of inflammatory cytokines and inhibition of reactive oxygen species. Additionally, using an IL1β-induced insulin resistance 3T3-L1 cell model, upregulation of TST associated with antidiabetic effects. Therefore, we demonstrate that TST-mediated suppression of the inflammatory response protects in vitro cell model of white adipocytes from insulin resistance-induced inflammation. These results encourage the development of potent medicines in the future that specifically target TST in the fat tissue, which could lead to new ways of treating diabetes associated with obesity.