title: Effect of bilirubin on triglyceride synthesis in streptozotocin-induced diabetic nephropathy.
abstract: We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-β1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXRα, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXRα and SREBP-1 expression and oxidative stress.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jianwei
authors.identifier: 0000-0003-0044-4309
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Eun Seong
authors.identifier: 0000-0001-6237-9528
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Seon Ha
authors.identifier: 0000-0002-4188-7205
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Shin-Young
authors.identifier: 0000-0002-6844-0614
authors.initials: SY
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sejoong
authors.identifier: 0000-0002-7238-9962
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ki Young
authors.identifier: 0000-0002-8872-8236
authors.initials: KY
authors.lastname: Na
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Wan
authors.identifier: 0000-0001-9401-892X
authors.initials: DW
authors.lastname: Chae
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Immunology, Seoul National University Postgraduate School, Seoul, Korea. ; Renal Institute, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Ho Jun
authors.identifier: 0000-0003-1185-2631
authors.initials: HJ
authors.lastname: Chin
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003401:Creatine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D007668:Kidney / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D014280:Triglycerides / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood
chemical_list: D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D017382:Reactive Oxygen Species; D014280:Triglycerides; D013311:Streptozocin; D019255:NADPH Oxidases; D003401:Creatine; D001663:Bilirubin
keywords: Bilirubin; Diabetes-Related Complications; Fibrosis; Transforming Growth Factor beta; Triglyceride