RGD Reference Report - Upregulation of hepatic LRP1 by rosiglitazone: a possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia. - Rat Genome Database

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Upregulation of hepatic LRP1 by rosiglitazone: a possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia.

Authors: Moon, Jae Hoon  Kim, Hyung Jun  Kim, Hyun Min  Yang, Ae Hee  Lee, Byung-Wan  Kang, Eun Seok  Lee, Hyun Chul  Cha, Bong Soo 
Citation: Moon JH, etal., J Mol Endocrinol. 2012 Oct 10;49(3):165-74. doi: 10.1530/JME-12-0119. Print 2012 Dec.
RGD ID: 13800521
Pubmed: PMID:22889684   (View Abstract at PubMed)
DOI: DOI:10.1530/JME-12-0119   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LRP1Humandiabetes mellitus treatmentISOLrp1 (Rattus norvegicus) RGD 
Lrp1Ratdiabetes mellitus treatmentIDA  RGD 
Lrp1Mousediabetes mellitus treatmentISOLrp1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lrp1  (LDL receptor related protein 1)

Genes (Mus musculus)
Lrp1  (low density lipoprotein receptor-related protein 1)

Genes (Homo sapiens)
LRP1  (LDL receptor related protein 1)


Additional Information