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• W2886969890 abstract "BackgroundMitochondrial pyruvate import via mitochondrial pyruvate carrier (MPC) is a central step in hepatic gluconeogenesis. Berberine inhibits hepatic gluconeogenesis, but the mechanism is incompletely understood. This study aims to investigate whether berberine could reduce excessive hepatic glucose production (HGP) by limiting mitochondrial import of pyruvate through MPC1.MethodsHigh-fat diet (HFD) feeding augmented HGP. The effects of berberine on hepatic fatty acid oxidation, sirtuin3 (SIRT3) induction and mitochondrial pyruvate carrier 1 (MPC1) function were examined.FindingsHFD feeding increased hepatic acetyl coenzyme A (acetyl CoA) accumulation with impaired pyruvate dehydrogenase (PDH) activity and increased pyruvate carboxylase (PC) induction. Berberine reduced acetyl CoA accumulation by limiting fatty acid oxidation and prevented mitochondrial pyruvate shift from oxidation to gluconeogenesis through carboxylation. Upon pyruvate response, SIRT3 binded to MPC1 and stabilized MPC1 protein via deacetylation modification, facilitating mitochondrial import of pyruvate. Berberine preserved the acetylation of MPC1 by suppression of SIRT3 induction and impaired MPC1 protein stabilization via protein degradation, resultantly limiting mitochondrial pyruvate supply for gluconeogenesis.InterpretationBerberine reduced acetyl CoA contents by limiting fatty acid oxidation and increased MPC1 degradation via preserving acetylation, thereby restraining HGP by blocking mitochondrial import of pyruvate. These findings suggest that limitation of mitochondrial pyruvate import might be a therapeutic strategy to prevent excessive hepatic glucose production." @default.
• W2886969890 created "2018-08-22" @default.
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• W2886969890 date "2018-08-01" @default.
• W2886969890 modified "2023-09-28" @default.
• W2886969890 title "Berberine Reduces Pyruvate-driven Hepatic Glucose Production by Limiting Mitochondrial Import of Pyruvate through Mitochondrial Pyruvate Carrier 1" @default.
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• W2886969890 doi "https://doi.org/10.1016/j.ebiom.2018.07.039" @default.
• W2886969890 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6117739" @default.
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