title: ERK-dependent mTOR pathway is involved in berberine-induced autophagy in hepatic steatosis.
abstract: Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem and is considered as a hepatic manifestation of metabolic syndrome. Increasing evidence demonstrates that berberine (BBR), a natural plant alkaloid, is beneficial for obesity-associated NAFLD. However, the mechanisms about how BBR improves hepatic steatosis remain uncertain. Recently, some reports revealed that enhanced autophagy could decrease hepatic lipid accumulation. In this study, we first established a high-fed diet (HFD) mice model and oleate-palmitate-induced lipotoxicity hepatocytes to explore the association among BBR, autophagy and hepatic steatosis. Our data demonstrated that BBR had profound effects on improving hepatic lipid accumulation both in vivo and in vitro, and led to high autophagy flux. The molecular alterations proceeding these changes were characterized by inhibition of the ERK/mTOR pathway. These findings suggest an important mechanism for the positive effects of BBR on hepatic steatosis, and may provide new evidence for the clinical use of BBR in NAFLD.
authors.affiliation: Department of Endocrine and MetabolismQilu Hospital of Shandong University, Shandong University, Ji'nan, Shandong, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Endocrine and MetabolismQilu Hospital of Shandong University, Shandong University, Ji'nan, Shandong, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Mei
authors.affiliation: Department of Endocrine and MetabolismQilu Hospital of Shandong University, Shandong University, Ji'nan, Shandong, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Sha
authors.affiliation: Department of Endocrine and MetabolismQilu Hospital of Shandong University, Shandong University, Ji'nan, Shandong, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Endocrine and MetabolismJiaxiang People's Hospital, Ji'ning, Shandong, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrine and MetabolismQilu Hospital of Shandong University, Shandong University, Ji'nan, Shandong, China dr_dongming@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D001835:Body Weight; D002460:Cell Line; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D008055:Lipids; D001599:Berberine; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose
keywords: ERK; autophagy; berberine; hepatic steatosis; mTOR