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7336380 
Journal Article 
Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway 
Zhu, X; Bian, H; Wang, L; Sun, X; Xu, X; Yan, H; Xia, M; Chang, X; Lu, Y; Li, Y; Xia, P; Li, X; Gao, X 
2019 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
Elsevier Inc. 
141 
192-204 
English 
Background: Berberine (BBR), a natural compound extracted from Chinese herb, has been shown to effectively attenuate nonalcoholic fatty liver disease (NAFLD) in clinic. However, the mechanism underlying the effect of BBR is not fully understood. Stearyl-coenzyme A desaturase 1 (SCD1) mediates lipid metabolism in liver. Therefore, we hypothesized that SCD1 mediated the beneficial effect of BBR on NAFLD. Methods: The expression of SCD1 was measured in the liver of NAFLD patients and ob/ob mice. The effect of BBR on NAFLD was evaluated in C57BL/6 J mice on high fat diet (HFD). The effect of BBR was also investigated in HepG2 and AML12 cells exposed to high glucose and palmitic acid. Oil red O staining was performed to detect triglyceride (TG) level. Quantitative real-time polymerase chain reaction and Western blot were used to detect the messenger ribonucleic acid (mRNA) and protein expression of target genes. The activity of SCD1 promoter was measured by dual-luciferase reporter assay. Results: The expression of SCD1 was increased in the liver of NAFLD patients and ob/ob mice. BBR reduced hepatic TG accumulation and decreased the expressions of hepatic SCD1 and other TG synthesis related genes both in vivo and in vitro. Knockdown of SCD1 expression mimicked the effect of BBR decreasing TG level in steatotic hepatocytes, whereas overexpression of SCD1 attenuated the effect of BBR. Mechanistically, BBR promoted the phosphorylation of AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein-1c (SREBP-1c) in HepG2 cells and the liver of HFD-fed mice. Activation of the AMPK-SREBP-1c pathway and sterol regulatory element (SRE) motif in SCD1 promoter (−920/-550) was responsible for the BBR-induced suppression of SCD1. Conclusion: BBR reduces liver TG synthesis and attenuates hepatic steatosis through the activation of AMPK-SREBP-1c-SCD1 pathway. © 2019 Elsevier Inc. 
AMP-activated protein kinase; AMPK; Berberine; NAFLD; Nonalcoholic fatty liver disease; SCD1; SREBP-1c; Stearyl-coenzyme A desaturase 1; Sterol regulatory element-binding protein-1c; acyl coenzyme A desaturase; berberine; glucose; hydroxymethylglutaryl coenzyme A reductase kinase; messenger RNA; palmitic acid; stearyl coenzyme A desaturase 1; sterol regulatory element binding protein 1c; triacylglycerol; unclassified drug; acyl coenzyme A desaturase; berberine; hydroxymethylglutaryl coenzyme A reductase kinase; insulin; SCD1 protein, human; Scd1 protein, mouse; SREBF1 protein, human; Srebf1 protein, mouse; sterol regulatory element binding protein 1; AML12 cell line; animal cell; animal experiment; animal model; animal tissue; Article; C57BL 6 mouse; controlled study; dual luciferase reporter assay; enzyme activity; enzyme phosphorylation; gene expression; gene knockdown; gene overexpression; genetic transcription; Hep-G2 cell line; human; human cell; human tissue; in vitro study; in vivo study; lipid diet; liver cell; luciferase assay; male; mouse; nonalcoholic fatty liver; nonhuman; ob/ob mouse; oil red O staining; priority journal; promoter region; protein expression; protein metabolism; protein motif; quantitative analysis; real time polymerase chain reaction; staining; sterol regulatory element motif; triacylglycerol level; Western blotting; animal; biopsy; C57BL mouse; fatty liver; glucose tolerance test; lipid metabolism; liver; metabolism; mouse mutant; nonalcoholic fatty liver; AMP-Activated Protein Kinases; Animals; Berberine; Biopsy; Fatty Liver; Glucose Tolerance Test; Hep G2 Cells; Humans; Insulin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1