title: A Jak2 inhibitor, AG490, reverses lipin-1 suppression by TNF-alpha in 3T3-L1 adipocytes.
abstract: 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.
authors.affiliation: Department of General Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Sachie
authors.initials: S
authors.lastname: Tanno
authors.forename: Masumi
authors.initials: M
authors.lastname: Ohhira
authors.forename: Wataru
authors.initials: W
authors.lastname: Motomura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanno
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takakusaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Okumura
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis*; D009765:Obesity / Q000378:metabolism*; D010711:Phosphatidate Phosphatase; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase