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-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.