title: High-fat diet causes increased serum insulin and glucose which synergistically lead to renal tubular lipid deposition and extracellular matrix accumulation.
abstract: Renal tubular lipid accumulation is associated with renal injury in the metabolic syndrome, but its mechanisms are not fully elucidated. The purpose of the present study was to investigate the exact mechanism of renal tubular lipid accumulation in the diet-induced metabolic syndrome. The in vivo experiments showed that a high-fat diet induced hyperglycaemia, hyperinsulinaemia and hypertriacylglycerolaemia, subsequent increases in sterol regulatory element binding protein-1 (SREBP-1) and transforming growth factor-β1 (TGF-β1), lipid droplet deposit in renal tubular cells and interstitial extracellular matrix accumulation in Wistar rats. A human renal proximal tubular epithelial cell line (HKC) was used to determine the direct role of insulin, and the results revealed that insulin induced SREBP-1, fatty acid synthase (FASN), TGF-β1 expressions, lipid droplet and extracellular matrix deposits. Knockdown of SREBP-1 by RNA interference technology significantly inhibited FASN, TGF-β1 up-regulation, lipid and extracellular matrix accumulation caused by insulin. In addition, we found that insulin and high glucose could synergistically increase SREBP-1, FASN, TGF-β1 and fibronectin expressions in HKC cells. These results indicate that high-fat diet-induced increased serum insulin and glucose synergistically cause renal tubular lipid deposit and extracellular matrix accumulation via the SREBP-1 pathway.
authors: Department of Pathology, Hebei Medical University, NO361 Zhongshan East Road, Shijiazhuang City, Hebei Province, People's Republic of China.
authors: Jun
authors: J
authors: Hao
authors: Shu-Xia
authors: SX
authors: Liu
authors: Song
authors: S
authors: Zhao
authors: Qing-Juan
authors: QJ
authors: Liu
authors: Wei
authors: W
authors: Liu
authors: Hui-Jun
authors: HJ
authors: Duan
mesh_terms: D000818:Animals; D002460:Cell Line; D004041:Dietary Fats / Q000009:adverse effects*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism; D008297:Male; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000209:etiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005353:Fibronectins; D007328:Insulin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051780:Sterol Regulatory Element Binding Protein 1; D053773:Transforming Growth Factor beta1; D064429:Fatty Acid Synthases