摘要：SummaryObesity is an important risk factor and a potential treatment target for hepatic steatosis. The maladaptation of hepatic mitochondrial flexibility plays a key role in the hepatic steatosis. Herein, we found that hepatocyte-like cells derived from human adipose stem cell of obese patients exhibited the characteristics of hepatic steatosis and accompanied with lower expression of the subunits of mitochondrial complex I and lower oxidative phosphorylation levels. The GSK3 inhibitor CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I, the basal oxygen consumption rate, and the fatty acid oxidation of the hepatocytes of obese patients by upregulating the expression of the transcription factor PGC-1α, TFAM, and NRF1 involved in mitochondrial biogenesis. Moreover, CHIR-99021 decreased the lipid droplets size and the triglyceride levels in hepatocytes of obese patients. The results demonstrate that GSK3 inhibition ameliorates hepatic steatosis by elevating the mitochondrial function in hepatocytes of obese patients.Graphical abstractDisplay OmittedHighlights•Obese patients’ adipose-stem-cell-derived hepatocytes reveal hepatic steatosis•Hepatic steatosis is accompanied the mitochondrial dysfunction•The mitochondrial dysfunction is governed by the low expression PGC-1α, TFAM, and NRF1•GSK3 inhibitor ameliorates hepatic steatosis via mitochondrial dysfunction modulationhuman metabolism; molecular biology
