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

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概要

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• 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.

著者

• ZHU Hua

  Department of Chemistry, Nanjing University

• HUANG Lan

  Department of Chemistry, Peking University

• Li Guo-Sheng

  Department of Pathology, First Affiliated Hospital of Dalian Medical University

• Liu Xu-Han

  Department of Endocrinology, Dalian Municipal Central Hospital

• Liu Ya-Li

  Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences

• Ma Chun-Mei

  Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences

• Qin Chuan

  Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences

• Zhu Hua

  Department Of Chemistry Nanjing University

• Qin Chuan

  Department Of Pathology Institute Of Laboratory Animal Science Chinese Academy Of Medical Science &a

• Liu Ya-Li

  Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

• HUANG Lan

  Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

• Qin Chuan

  Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

• Ma Chun-Mei

  Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

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