1. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.
- Author
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Liu J, Dong H, Zhang Y, Cao M, Song L, Pan Q, Bulmer A, Adams DB, Dong X, and Wang H
- Subjects
- Adiponectin metabolism, Animals, Blood Glucose analysis, Body Weight drug effects, Diet, High-Fat, Disease Models, Animal, Glucose Tolerance Test, Insulin Resistance, Leptin metabolism, Lipid Metabolism drug effects, Lipids blood, Liver drug effects, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Obesity etiology, PPAR gamma genetics, Receptor, Insulin genetics, Receptor, Insulin metabolism, Sterol Regulatory Element Binding Protein 1 genetics, Sterol Regulatory Element Binding Protein 1 metabolism, Adipokines metabolism, Bilirubin pharmacology, Cholesterol metabolism, PPAR gamma metabolism
- Abstract
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.
- Published
- 2015
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