The hepatic compensatory response to elevated systemic sulfide promotes diabetes.
Cell Rep
; 37(6): 109958, 2021 11 09.
Article
en En
| MEDLINE
| ID: mdl-34758301
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sulfuros
/
Tiosulfato Azufretransferasa
/
Diabetes Mellitus
/
Dislipidemias
/
Gluconeogénesis
/
Hígado
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido