Upregulation of hepatic LRP1 by rosiglitazone

A possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia

Jae Hoon Moon, Hyung Jun Kim, Hyun Min Kim, Ae Hee Yang, byungwan lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Hepatic LDL 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 rosiglitazone in HepG2 cells. However, at concentrations above 50 μM rosiglitazone, LRP1 mRNA and protein expressions did not change compared with those in nontreated cells. Reporter assay showed that 0.5 and 5 μM rosiglitazone increased the transcriptional activity of the LRP1 promoter in HepG2 cells. The uptake of apolipoprotein E through LRP1 in HepG2 cells was also increased by rosiglitazone. Hepatic LRP1 was reduced in OLETF rats compared with that of LETO rats and rosiglitazone treatment increased hepatic LRP1 in OLETF rats. A high glucose condition (25 mM 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 contribute to an improvement in atherogenic lipid profiles in diabetic patients.

Original languageEnglish
Pages (from-to)165-174
Number of pages10
JournalJournal of Molecular Endocrinology
Volume49
Issue number3
DOIs
Publication statusPublished - 2012 Dec 1

Fingerprint

rosiglitazone
Low Density Lipoprotein Receptor-Related Protein-1
Thiazolidinediones
Dyslipidemias
Up-Regulation
Inbred OLETF Rats
Liver
Hep G2 Cells

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Molecular Biology

Cite this

Moon, Jae Hoon ; Kim, Hyung Jun ; Kim, Hyun Min ; Yang, Ae Hee ; lee, byungwan ; Kang, Eun Seok ; Lee, Hyun Chul ; Cha, Bong Soo. / Upregulation of hepatic LRP1 by rosiglitazone : A possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia. In: Journal of Molecular Endocrinology. 2012 ; Vol. 49, No. 3. pp. 165-174.
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abstract = "Hepatic LDL 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 rosiglitazone in HepG2 cells. However, at concentrations above 50 μM rosiglitazone, LRP1 mRNA and protein expressions did not change compared with those in nontreated cells. Reporter assay showed that 0.5 and 5 μM rosiglitazone increased the transcriptional activity of the LRP1 promoter in HepG2 cells. The uptake of apolipoprotein E through LRP1 in HepG2 cells was also increased by rosiglitazone. Hepatic LRP1 was reduced in OLETF rats compared with that of LETO rats and rosiglitazone treatment increased hepatic LRP1 in OLETF rats. A high glucose condition (25 mM 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 contribute to an improvement in atherogenic lipid profiles in diabetic patients.",
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Upregulation of hepatic LRP1 by rosiglitazone : A possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia. / Moon, Jae Hoon; Kim, Hyung Jun; Kim, Hyun Min; Yang, Ae Hee; lee, byungwan; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo.

In: Journal of Molecular Endocrinology, Vol. 49, No. 3, 01.12.2012, p. 165-174.

Research output: Contribution to journalReview article

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T1 - Upregulation of hepatic LRP1 by rosiglitazone

T2 - A possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia

AU - Moon, Jae Hoon

AU - Kim, Hyung Jun

AU - Kim, Hyun Min

AU - Yang, Ae Hee

AU - lee, byungwan

AU - Kang, Eun Seok

AU - Lee, Hyun Chul

AU - Cha, Bong Soo

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