Apr 29, 2020

The hepatic compensatory response to elevated systemic sulfide impairs medium chain fat oxidation and promotes diabetes

BioRxiv : the Preprint Server for Biology
R. N. CarterNicholas M Morton

Abstract

Impaired hepatic glucose and lipid metabolism are hallmarks of type 2 diabetes. Increased sulfide production from cysteine, 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 sulfur transferase (Tst ko mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia and fatty liver, despite wholebody insulin sensitisation. Unexpectedly, hepatic sulfide levels were normal in Tst ko mice, a result of homeostatic induction of mitochondrial sulfide disposal and glutathione excretion associated with net suppression of protein persulfidation and nuclear respiratory factor 2 target proteins. Proteomic and persulfidomic profiling converged on hepatic lipid metabolism, revealing a deficit in medium chain fatty acid oxidation in Tst ko mice. In conclusion our findings have implications for sulfide donor strategies in the context of liver function and metabolic disease.

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Research
Decision Making
Electroencephalography
Magnetic Resonance Imaging
Exons
Clinical Researcher
Brain
Psychiatric Inpatient
Clinical Decision-Making
Research Personnel

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.