PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes
| Autor: | Paul Webb, Ivan da Rocha Pitta, Angélica Amorim Amato, Flora Aparecida Milton, Anithachristy S. Arumanayagam, Douglas H. Sieglaff, Aleksandra Cvoro, Carly S. Filgueira, Francisco de Assis Rocha Neves, Maria do Carmo Alves de Lima |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class medicine.medical_treatment Biophysics Gene Expression Biology Biochemistry Partial agonist Rosiglitazone Mice Insulin resistance 3T3-L1 Cells Internal medicine Adipocytes medicine Animals Hypoglycemic Agents Thiazolidinedione Receptor Molecular Biology Psychological repression Adipogenesis Insulin 3T3-L1 Cell Biology medicine.disease PPAR gamma Endocrinology Thiazolidinediones Insulin Resistance medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 464:718-723 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2015.07.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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