| First Author | Carter RN | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 6 | Pages | 109958 |
| PubMed ID | 34758301 | Mgi Jnum | J:320330 |
| Mgi Id | MGI:6870564 | Doi | 10.1016/j.celrep.2021.109958 |
| Citation | Carter RN, et al. (2021) The hepatic compensatory response to elevated systemic sulfide promotes diabetes. Cell Rep 37(6):109958 |
| abstractText | Impaired hepatic glucose and lipid metabolism are hallmarks of type 2 diabetes. Increased sulfide production or sulfide donor compounds may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range. We show that mice lacking the liver- enriched mitochondrial SOP enzyme thiosulfate sulfurtransferase (Tst(-/-) mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia, and fatty liver. Unexpectedly, hepatic sulfide levels are normal in Tst(-/-) mice because of exaggerated induction of sulfide disposal, with associated suppression of global protein persulfidation and nuclear respiratory factor 2 target protein levels. Hepatic proteomic and persulfidomic profiles converge on gluconeogenesis and lipid metabolism, revealing a selective deficit in medium-chain fatty acid oxidation in Tst(-/-) mice. We reveal a critical role of TST in hepatic metabolism that has implications for sulfide donor strategies in the context of metabolic disease. |
