title: Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.
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.
authors.affiliation: College of Animal Science and Veterinary Medicine, Qingdao Agricultural University, P.R. China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Huansheng
authors.initials: H
authors.lastname: Dong
authors.affiliation: 1] Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA [2] Colleges of Life Sciences, Qingdao Agricultural University, Qingdao, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Veterinary Medicine, Qingdao, P.R. China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Cao
authors.affiliation: 1] College of Animal Science and Veterinary Medicine, Qingdao, P.R. China [2] Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Song
authors.affiliation: College of Animal Science and Veterinary Medicine, Qingdao, P.R. China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Pan
authors.affiliation: School of Medical Science, Griffith University, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bulmer
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Adams
authors.affiliation: Colleges of Life Sciences, Qingdao Agricultural University, Qingdao, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D054392:Adipokines; D052242:Adiponectin; D001786:Blood Glucose; D020738:Leptin; D008055:Lipids; D047495:PPAR gamma; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D002784:Cholesterol; D011972:Receptor, Insulin; D001663:Bilirubin