title: Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity.
abstract: Increasing evidence demonstrates that berberine (BBR) is beneficial for obesity-associated non-alcoholic fatty liver disease (NAFLD). However, it remains to be elucidated how BBR improves aspects of NAFLD. Here we revealed an AMP-activated protein kinase (AMPK)-independent mechanism for BBR to suppress obesity-associated inflammation and improve hepatic steatosis. In C57BL/6J mice fed a high-fat diet (HFD), treatment with BBR decreased inflammation in both the liver and adipose tissue as indicated by reduction of the phosphorylation state of JNK1 and the mRNA levels of proinflammatory cytokines. BBR treatment also decreased hepatic steatosis, as well as the expression of acetyl-CoA carboxylase and fatty acid synthase. Interestingly, treatment with BBR did not significantly alter the phosphorylation state of AMPK in both the liver and adipose tissue of HFD-fed mice. Consistently, BBR treatment significantly decreased the phosphorylation state of JNK1 in both hepatoma H4IIE cells and mouse primary hepatocytes in both dose-dependent and time-dependent manners, which was independent of AMPK phosphorylation. BBR treatment also caused a decrease in palmitate-induced fat deposition in primary mouse hepatocytes. Taken together, these results suggest that BBR actions on improving aspects of NAFLD are largely attributable to BBR suppression of inflammation, which is independent of AMPK.
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Shih-Lung
authors.initials: SL
authors.lastname: Woo
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Honggui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.|Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Botchlett
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Ya
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.|Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Hepatology, Hospital of Chinese Medicine of Hubei, Hubei University of Chinese Medicine, Hubei 430060, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qifu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.|The Laboratory of Lipid &Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.|Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis; D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000096:biosynthesis; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D004041:Dietary Fats; D001599:Berberine; D054890:Fatty Acid Synthase, Type I; D048055:Mitogen-Activated Protein Kinase 8; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase