Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/6436
Title: PPARγ partial agonist GQ-16strongly represses a subset of genes in 3T3-L1 adipocytes
Authors: Milton, Flora Aparecida
Čvoro, Aleksandra 
Amato, Angelica A.
Sieglaff, Douglas H.
Filgueira, Carly S.
Arumanayagam, Anithachristy Sigamani
do Carmo Alves de Lima, Maria
Rocha Pitta, Ivan
de Assis Rocha Neves, Francisco
Webb, Paul
Keywords: 3T3-L1;;Gene expression;;Partial agonist;;Peroxisome proliferator activated receptor γ;;Repression;;Thiazolidinedione.
Issue Date: 28-Aug-2015
Rank: M22
Publisher: Academic Press
Journal: Biochemical and Biophysical Research Communications
Volume: 464
Issue: 3
Start page: 718
End page: 723
Abstract: 
Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1 adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16.
URI: https://biore.bio.bg.ac.rs/handle/123456789/6436
DOI: 10.1016/j.bbrc.2015.07.011
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