Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism.

Abstract:

:The PPARγ nuclear receptor regulates the expression of genes involved in lipid and carbohydrate metabolism, and it has protective effects in some patients with type 2 diabetes. Nevertheless, the therapeutic value of the PPARγ nuclear receptor protein is limited due to the secondary effects of some PPARγ ligands. Because the downstream effects of PPARγ are determined by the binding of specific cofactors that are mediated by ligand-induced conformational changes, we evaluated the differential effects of various ligands on the binding of certain cofactors associated with PPARγ. The ligands used were rosiglitazone for treating type 2 diabetes and telmisartan for treating arterial hypertension. Functional, phenotypic, and molecular studies were conducted on pre-adipocyte 3T3-L1 and functional studies in U2OS cells. The moderating influence of various cofactor families was evaluated using transient transfection assays. Our findings confirm that telmisartan has a partial modulating effect on PPARγ activity compared to rosiglitazone. The cofactors SRC1 and GRIP1 mediate the activity of telmisartan and rosiglitazone and partially determine the difference in their effects. Studying the modulating activity of these cofactors can provide interesting insights for developing new therapeutic approaches for certain metabolic diseases.

journal_name

Genet Mol Biol

authors

Lizcano F,Vargas D

doi

10.1590/S1415-47572013005000002

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

134-9

issue

1

eissn

1415-4757

issn

1678-4685

pii

gmb-36-134

journal_volume

36

pub_type

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