A Jak2 inhibitor, AG490, reverses lipin-1 suppression by TNF-α in 3T3-L1 adipocytes
| Autor: | Masumi Ohhira, Satoshi Tanno, Yoshihiro Tsuchiya, Toshikatsu Okumura, Takayuki Yoshizaki, Kaoru Takakusaki, Nobuhiko Takahashi, Wataru Motomura, Sachie Tanno, Yutaka Kohgo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Ceramide
medicine.medical_specialty Biophysics Phosphatidate Phosphatase Adipose tissue Biology Biochemistry Pathogenesis chemistry.chemical_compound Mice Insulin resistance Internal medicine 3T3-L1 Cells Coactivator Transcriptional regulation medicine Animals Obesity RNA Messenger Molecular Biology Protein Kinase Inhibitors Tumor Necrosis Factor-alpha Nuclear Proteins 3T3-L1 Cell Biology Janus Kinase 2 Tyrphostins medicine.disease Endocrinology chemistry Adipogenesis |
| Zdroj: | Biochemical and Biophysical Research Communications. 382(2):348-352 |
| ISSN: | 0006-291X |
| Popis: | http://dx.doi.org/10.1016/j.bbrc.2009.03.021 Lipin-1 is a multifunctional metabolic regulator, involving in triacylglycerol and bioactive glycerolipids synthesis as an enzyme, transcriptional regulation as a coactivator, and adipogenesis. In obesity, adipose lipin-1 expression is decreased. Although lipin-1 is implicated in the pathogenesis of obesity, the mechanism is still not clear. Since TNF-α is deeply involved in the pathogenesis of obesity, insulin resistance, and diabetes, here we investigated the role of TNF-α on lipin-1 expression in adipocytes. Quantitative PCR studies showed that TNF-α suppressed both lipin-1A and -1B isoform expression in time- and dose-dependent manners in mature 3T3-L1 adpocytes. A Jak2 inhibitor, AG490, reversed the suppressive effect of TNF-α on both lipin-1A and -1B. In contrast, NF-κB, MAPKs, ceramide, and β-catenin pathway tested were not involved in the mechanism. These results suggest that TNF-α could be involved in obesity-induced lipin-1 suppression in adipocytes and Jak2 may play an important role in the mechanism. |
| Databáze: | OpenAIRE |
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