TY - JOUR
T1 - Effect of bilirubin on triglyceride synthesis in streptozotocin-induced diabetic nephropathy
AU - Xu, Jianwei
AU - Lee, Eun Seong
AU - Baek, Seon Ha
AU - Ahn, Shin Young
AU - Kim, Sejoong
AU - Na, Ki Young
AU - Chae, Dong Wan
AU - Chin, Ho Jun
N1 - Publisher Copyright:
© 2014 The Korean Academy of Medical Sciences.
PY - 2014
Y1 - 2014
N2 - 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 LXRa and SREBP-1 expression and oxidative stress.
AB - 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 LXRa and SREBP-1 expression and oxidative stress.
KW - Bilirubin
KW - Diabetes-related complications
KW - Fibrosis
KW - Transforming growth factor beta
KW - Triglyceride
UR - http://www.scopus.com/inward/record.url?scp=84930983404&partnerID=8YFLogxK
U2 - 10.3346/jkms.2014.29.S2.S155
DO - 10.3346/jkms.2014.29.S2.S155
M3 - Article
C2 - 25317020
AN - SCOPUS:84930983404
SN - 1011-8934
VL - 29
SP - S155-S163
JO - Journal of Korean Medical Science
JF - Journal of Korean Medical Science
ER -