PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

Flora Aparecida Milton, Aleksandra Cvoro, Angelica A. Amato, Douglas H. Sieglaff, Carly S. Filgueira, Anithachristy Sigamani Arumanayagam, Maria Do Carmo Alves De Lima, Ivan Rocha Pitta, Francisco De Assis Rocha Neves, Paul Webb

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number34219
Pages (from-to)718-723
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume464
Issue number3
DOIs
StatePublished - Aug 7 2015

Keywords

  • 3T3-L1
  • Gene expression
  • Partial agonist
  • Peroxisome proliferator activated receptor γ
  • Repression
  • Thiazolidinedione

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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