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Up-regulation of hepatic LRP1 by rosiglitazone: a possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia.
MedLine Citation:
PMID:  22889684     Owner:  NLM     Status:  Publisher    
Hepatic low-density lipoprotein receptor-related protein 1 (LRP1) plays a role in the clearance of circulating remnant lipoproteins. In this study, we investigated the effect of rosiglitazone treatment on the expression and function of hepatic LRP1. HepG2 cells were incubated with various concentrations of rosiglitazone. Male Long-Evans Tokushima Otsuka (LETO) rats and Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats were treated with rosiglitazone for 5 weeks. The expression and function of LRP1 in HepG2 cells and liver samples of rats were analyzed. LRP1 mRNA and protein expressions were increased by 0.5 and 5 μM of rosiglitazone in HepG2 cells. However, at concentrations above 50 μM of rosiglitazone, LRP1 mRNA and protein expressions did not change compared to those in non-treated cells. Reporter assay showed that 0.5 and 5 μM of rosiglitazone increased the transcriptional activity of the LRP1 promoter in HepG2 cells. The uptake of ApoE through LRP1 in HepG2 cells was also increased by rosiglitazone. Hepatic LRP1 was reduced in OLETF rats compared to that of LETO rats and rosiglitazone treatment increased hepatic LRP1 in OLETF rats. A high glucose condition (25 mM of glucose in culture media) reduced the expression of LRP1 in HepG2 cells, and this reduced LRP1 expression was recovered with rosiglitazone. In conclusion, our data suggest that decreased hepatic LRP1 in a diabetic condition is associated with the development of atherogenic dyslipidemia and that increased hepatic LRP1 by thiazolidinediones could contributes to an improvement in atherogenic lipid profiles in diabetic patients.
Jae Hoon Moon; Hyung Jun Kim; Hyun Min Kim; Ae Hee Yang; Byung-Wan Lee; Eun Seok Kang; Hyun Chul Lee; Bong Soo Cha
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-13
Journal Detail:
Title:  Journal of molecular endocrinology     Volume:  -     ISSN:  1479-6813     ISO Abbreviation:  J. Mol. Endocrinol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8902617     Medline TA:  J Mol Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
J Moon, Department of Internal Medicine, Seoul Nationl University Bundang Hospital, Seongnam-si, 463-707, Korea, Republic of.
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