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THRAP3 depletion reduces PPARγ mRNA and anti-inflammatory action in 3T3-L1 adipocytes
- Source :
- Journal of Molecular Endocrinology. 67:149-159
- Publication Year :
- 2021
- Publisher :
- Bioscientifica, 2021.
-
Abstract
- Peroxisome proliferator-activated receptor γ (PPARγ) is the master transcriptional regulator of adipocytes and the cellular target of thiazolidinedione (TZD) drugs. Suppression of pro-inflammatory actions, including pro-inflammatory gene expression and lipolysis in adipocytes, contributes to PPARγ-mediated anti-diabetic effects of TZDs. However, adverse side effects largely limited the clinical use of TZDs, despite their potent insulin-sensitizing effects. Therefore, it is important to understand how PPARγ is regulated. Thyroid hormone receptor-associated protein 3 (THRAP3) was previously reported to promote diabetic gene expression by acting as a transcriptional coregulator of PPARγ in adipocytes. Therefore, we tested if THRAP3 modulated anti-inflammatory functions of PPARγ in 3T3-L1 adipocytes. THRAP3 depletion increased basal and tumor necrosis factor α (TNFα)-induced lipolysis, pro-inflammatory gene expression, and phosphorylation of extracellular signal-regulated kinases (ERKs), suggesting elevated pro-inflammatory response after THRAP3 depletion in adipocytes. Moreover, TZD-mediated suppression of TNFα-induced lipolysis, pro-inflammatory gene expression, and ERK phosphorylation was attenuated or alleviated after THRAP3 depletion. Interestingly, the mRNA and protein levels of PPARγ were greatly reduced in THRAP3-depleted adipocytes. Actinomycin D treatment revealed that the stability of PPARγ mRNA was greatly reduced by THRAP3 depletion in adipocytes. Thus, in addition to modulating PPARγ function, THRAP3 may directly regulate the transcript of PPARγ in differentiated adipocytes.
- Subjects :
- medicine.drug_class
Lipolysis
RNA Stability
Mice
Endocrinology
3T3-L1 Cells
Gene expression
Adipocytes
Transcriptional regulation
medicine
Animals
RNA, Messenger
Phosphorylation
Thiazolidinedione
Receptor
Molecular Biology
Tumor Necrosis Factor-alpha
Chemistry
Kinase
Nuclear Proteins
3T3-L1
Cell biology
PPAR gamma
Gene Expression Regulation
Perilipins
Inflammation Mediators
Biomarkers
Transcription Factors
Subjects
Details
- ISSN :
- 14796813 and 09525041
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Endocrinology
- Accession number :
- edsair.doi.dedup.....079cfb9c08d170a524d42e77380879c0