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A Jak2 inhibitor, AG490, reverses lipin-1 suppression by TNF-α in 3T3-L1 adipocytes

pmid: 19281795
A Jak2 inhibitor, AG490, reverses lipin-1 suppression by TNF-α in 3T3-L1 adipocytes
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-alpha is deeply involved in the pathogenesis of obesity, insulin resistance, and diabetes, here we investigated the role of TNF-alpha on lipin-1 expression in adipocytes. Quantitative PCR studies showed that TNF-alpha 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-alpha on both lipin-1A and -1B. In contrast, NF-kappaB, MAPKs, ceramide, and beta-catenin pathway tested were not involved in the mechanism. These results suggest that TNF-alpha could be involved in obesity-induced lipin-1 suppression in adipocytes and Jak2 may play an important role in the mechanism.
Tumor Necrosis Factor-alpha, Phosphatidate Phosphatase, Nuclear Proteins, Janus Kinase 2, Tyrphostins, Mice, 3T3-L1 Cells, Animals, Obesity, RNA, Messenger, Protein Kinase Inhibitors
Tumor Necrosis Factor-alpha, Phosphatidate Phosphatase, Nuclear Proteins, Janus Kinase 2, Tyrphostins, Mice, 3T3-L1 Cells, Animals, Obesity, RNA, Messenger, Protein Kinase Inhibitors
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