title: Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver.
abstract: Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg-1·day-1 silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.
authors.affiliation: Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Yao
authors.forename: Min
authors.initials: M
authors.lastname: Zhi
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Pinjin
authors.initials: P
authors.lastname: Hu
authors.forename: Chujun
authors.initials: C
authors.lastname: Li
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D012838:Silymarin; D000077385:Silybin