Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.
Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.
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DOI：
10.1038/srep09886
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发表时间：
2015-05-28
影响因子：
4.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Liu J;Dong H;Zhang Y;Cao M;Song L;Pan Q;Bulmer A;Adams DB;Dong X;Wang H
肥胖会导致胰岛素抵抗和2型糖尿病。适度升高的胆红素水平有抗糖尿病的作用。本研究旨在确定胆红素治疗在饮食诱导肥胖(DIO)小鼠模型中降低肥胖和胰岛素抵抗的机制。给Dio小鼠灌胃胆红素或赋形剂14天。分别在治疗前、治疗后即刻和治疗后7周进行体重、血糖和胰岛素耐量试验。检测血脂、瘦素、脂联素、胰岛素、总胆红素和直接胆红素水平。用逆转录聚合酶链式反应和免疫印迹法检测肝脏中与脂肪代谢有关的激素调节元件结合蛋白1、胰岛素受体和PPARγ的表达。与对照组相比，胆红素治疗的小鼠体重、血糖水平、总胆固醇(TC)、瘦素、总胆红素和直接胆红素降低，脂联素增加，SREBP-1、IR和PPARγ基因表达增加。胆红素治疗的小鼠实现的代谢控制的改善是持久的：在治疗终止两个月后，胆红素治疗的DIO小鼠仍然对胰岛素敏感，瘦素水平较低，脂联素水平较高，同时PPARγ表达增加。这些结果表明，胆红素调节胆固醇代谢、脂肪因子和PPARγ水平，这可能有助于提高糖尿病小鼠的胰岛素敏感性和糖耐量。
Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice.
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