title: Berberine-improved visceral white adipose tissue insulin resistance associated with altered sterol regulatory element-binding proteins, liver x receptors, and peroxisome proliferator-activated receptors transcriptional programs in diabetic hamsters.
abstract: The diabetic "lipotoxicity" hypothesis presents that fat-induced visceral white adipose tissue insulin resistance plays a central role in the pathogenesis of type 2 diabetes. Berberine, a hypolipidemic agent, has been reported to have antidiabetic activities. The molecular mechanisms for this property are, however, not well clarified. Therefore in this study type 2 diabetic hamsters were induced by high-fat diet with low-dose streptozotocin. Then, we investigated the gene expression alterations and explored the molecular mechanisms underlying the therapeutic effect of berberine on fat-induced visceral white adipose tissue insulin resistance in diabetic hamsters by microarray analysis followed by real-time reverse transcription-polymerase chain reaction (RT-PCR) confirmation. Type 2 diabetic hamsters exhibited hyperglycemia and relative hyperinsulinemia, glucose intolerance, insulin resistance, intra-adipocyte lipid accumulation, significant increase in body weight and visceral white adipose tissue weight, abnormal serum adipokines levels, and deleterious dyslipidemia. Furthermore, they had increased sterol regulatory element-binding proteins (SREBPs) expression and decreased liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) expression in visceral white adipose tissue. After 9-week berberine treatment, fat-induced insulin resistance and diabetic phenotype in type 2 diabetic hamsters were significantly improved. Compared with diabetic hamsters, expression of LXRs and PPARs significantly increased and SREBPs significantly decreased in visceral white adipose tissue from berberine-treated diabetic hamsters. These results suggest that altered visceral white adipose tissue LXRs, PPARs, and SREBPs transcriptional programs are involved in the therapeutic mechanisms of berberine on fat-induced visceral white adipose tissue insulin resistance in type 2 diabetic hamsters.
authors.affiliation: Department of Pathology, First Affiliated Hospital of Dalian Medical University, Dalian, China. guoshengli998@163.com
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Li
authors.forename: Xu-Han
authors.initials: XH
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Ma
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001483:Base Sequence; D001599:Berberine / Q000494:pharmacology*; D006224:Cricetinae; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D007333:Insulin Resistance; D000071518:Liver X Receptors; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D051779:Sterol Regulatory Element Binding Proteins; D001599:Berberine