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High-fat diet causes increased serum insulin and glucose which synergistically lead to renal tubular lipid deposition and extracellular matrix accumulation.
MedLine Citation:
PMID:  21733321     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Jun Hao; Shu-Xia Liu; Song Zhao; Qing-Juan Liu; Wei Liu; Hui-Jun Duan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-28
Journal Detail:
Title:  The British journal of nutrition     Volume:  -     ISSN:  1475-2662     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-7-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372547     Medline TA:  Br J Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-12     Citation Subset:  -    
Affiliation:
Department of Pathology, Hebei Medical University, NO361 Zhongshan East Road, Shijiazhuang City, Hebei Province, People's Republic of China.
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