David PS
Member
Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing Syntaxin 17 homocysteinylation (Available online 9 July 2022)
•Highlights
Hyperhomocysteinimia is positively associated with NASH progression.
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Increased intrahepatic homocysteine causes NASH.
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STX17 homocysteinylation and ubiquitination leads to autophagy block during NASH progression.
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Vitamin B12 and folate supplementation restores STX17 protein expression and autophagy to decrease inflammation and fibrosis in NASH.
Lay summary
The roles of high serum homocysteine levels (HHcy) and intrahepatic homocysteine on the development of non-alcoholic seatohepatitis (NASH) are not known. We found HHcy increased with NASH severity and showed that homocysteinylation of the key autophagy protein STX17 led to autophagy block during NASH and NASH progression. Vitmains B12 and folate supplementation restored autophagy and reduced NASH progression and could be a new first-line therapy for NASH.