Curcumin decreases renal triglyceride accumulation through AMPK–SREBP signaling pathway in streptozotocin-induced type 1 diabetic rats

• Published in: The Journal of nutritional biochemistry Vol. 24; no. 5; pp. 796 - 802
• Main Authors: Soetikno, Vivian, Sari, Flori R, Sukumaran, Vijayakumar, Lakshmanan, Arun Prasath, Harima, Meilei, Suzuki, Kenji, Kawachi, Hiroshi, Watanabe, Kenichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2013
• Subjects: acetyl-CoA carboxylase; Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; adenosine monophosphate; administration & dosage; adverse effects; AMP-Activated Protein Kinases; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; blood; chemically induced; collagen; Curcumin; Curcumin - administration & dosage; Diabetes Mellitus, Experimental; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Diabetic Nephropathies; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - physiopathology; Diabetic nephropathy; droplets; drug effects; drug therapy; Dyslipidemia; extracellular matrix; Extracellular Matrix Proteins; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Fatty Acid Synthases; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; fatty-acid synthase; genetics; intraperitoneal injection; Kidney; Kidney - drug effects; Kidney - metabolism; kidneys; Male; Membrane Proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; metabolism; Perilipin-2; Phosphorylation; physiopathology; protein kinases; Rats; Rats, Sprague-Dawley; renal function; Signal Transduction; SREBP; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; Streptozocin; Streptozocin - adverse effects; Streptozotocin-induced diabetes; Transforming Growth Factor beta; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; transforming growth factors; Triglycerides; Triglycerides - blood; Triglycerides - metabolism; Vascular Endothelial Growth Factors; Vascular Endothelial Growth Factors - genetics; Vascular Endothelial Growth Factors - metabolism; Diabetic nephropathy; AMPK; Curcumin; SREBP; Dyslipidemia; Streptozotocin-induced diabetes
• ISSN: 0955-2863; 1873-4847; 1873-4847
• DOI: 10.1016/j.jnutbio.2012.04.013

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.