A Jak2 inhibitor, AG490, reverses lipin-1 suppression by TNF-alpha 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.
Tsuchiya
Yoshihiro
Y
Department of General Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
Takahashi
Nobuhiko
N
Yoshizaki
Takayuki
T
Tanno
Sachie
S
Ohhira
Masumi
M
Motomura
Wataru
W
Tanno
Satoshi
S
Takakusaki
Kaoru
K
Kohgo
Yutaka
Y
Okumura
Toshikatsu
T
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
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