title: Silibinin ameliorates steatosis and insulin resistance during non-alcoholic fatty liver disease development partly through targeting IRS-1/PI3K/Akt pathway.
abstract: Silibinin (SIL) is a well-studied hepato-protective agent against a spectrum of liver diseases. However, the role of SIL in non-alcoholic fatty liver disease (NAFLD) induced insulin resistance and underlying signaling is not fully characterized. In this study, Sprague-Dawley (SD) rats were fed with high-fat diet to develop NAFLD with or without an SIL co-treatment. NAFLD rats showed typical NAFLD symptoms including histological changes, insulin resistance, and glucose metabolism dysfunction. SIL co-treatment significantly ameliorated these pathological features partly through restoring the IRS-1/PI3K/Akt pathway. In addition, BRL-3A and HepG2 cells were incubated with palmitic acid (PA) to induce steatosis. SIL co-treatment in cells also reduced lipid accumulation, recovered cell viability, and down-regulated the protein expression of resistin, the marker for insulin resistance. Specific blocker of PI3K abolished the ameliorative effects of SIL on cellular steatosis. In conclusion, SIL alleviated steatosis and insulin resistance both in vivo and in vitro partly through regulating the IRS-1/PI3K/Akt pathway.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, PR China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Hai
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.forename: Yongli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sujuan
authors.initials: S
authors.lastname: Pei
authors.forename: Junbo
authors.initials: J
authors.lastname: Wang
authors.forename: Qinggui
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002460:Cell Line; D045744:Cell Line, Tumor; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D020011:Protective Agents; D012838:Silymarin; D000077385:Silybin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Insulin resistance; NAFLD; Signaling pathway; Silibinin