Curcumin decreases renal triglyceride accumulation through AMPK-SREBP signaling pathway in streptozotocin-induced type 1 diabetic rats.
Diabetic kidney disease has been associated with the presence of lipid deposits. We assumed that curcumin, a polyphenol, would attenuate the tissue dyslipidemic condition through activation of 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppression of sterol regulatory element-binding protein (SREBP)-1c in the kidney and would prevent renal progression in experimental type 1 diabetic rats. Diabetes was induced with streptozotocin (STZ) (55 mg/kg) by intraperitoneal injection in male Sprague-Dawley rats. Three weeks after STZ injection, rats were divided into three groups, namely, control, diabetic and diabetic treated with curcumin (100 mg/kg/day) by gavage for 8 weeks. We found that curcumin decreased plasma triglyceride and the amount of renal triglyceride significantly. Furthermore, treatment of diabetic rats with curcumin increased the phosphorylation of AMPK and prevented the increased renal expression of SREBP-1c and, as a result, decreased the expression of acetyl CoA carboxylase and fatty acid synthase as well as adipose differentiation-related protein, a marker of cytoplasmic droplets. We also demonstrate that curcumin significantly suppressed the increased expression of transforming growth factor β, vascular endothelial growth factor and extracellular matrix proteins such as type IV collagen and fibronectin. In addition, curcumin treatment increased nephrin expression to near-normal levels in diabetic rats. These results demonstrated that curcumin protects against the development of diabetic nephropathy through the AMPK-SREBP pathway and the reduction of renal triglyceride accumulation which could be a possible mechanism by which curcumin preserves renal function in diabetes.
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan.
Vivian
V
Soetikno
Flori R
FR
Sari
Vijayakumar
V
Sukumaran
Arun Prasath
AP
Lakshmanan
Meilei
M
Harima
Kenji
K
Suzuki
Hiroshi
H
Kawachi
Kenichi
K
Watanabe
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003474:Curcumin / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000070780:Perilipin-2; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D000070780:Perilipin-2; C000602984:Plin2 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D042442:Vascular Endothelial Growth Factors; C113267:nephrin; D013311:Streptozocin; D064429:Fatty Acid Synthases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D003474:Curcumin