Insulin and TNF alpha induce expression of the forkhead transcription factor gene Foxc2 in 3T3-L1 adipocytes via PI3K and ERK 1/2-dependent pathways

Molecular Endocrinology
Line M GrønningKjetil Taskén

Abstract

We have recently identified the winged helix/forkhead gene Foxc2 as a key regulator of adipocyte metabolism that counteracts obesity and diet-induced insulin resistance. This study was performed to elucidate the hormonal regulation of Foxc2 in adipocytes. We find that TNF alpha and insulin induce Foxc2 mRNA in differentiated 3T3-L1 cells with the kinetics of an immediate early response (1-2 h with 100 ng/ml insulin or 5 ng/ml TNF alpha). This induction is, in both cases, attenuated by the PI3K inhibitor wortmannin as well as the MAPK kinase inhibitor PD98059. Furthermore, we show that stimulation of 3T3-L1 adipocytes with phorbol-12-myristate-13-acetate or 8-(4-chlorophenyl)thio-cAMP induces the expression of Foxc2. Interestingly, we find that the basal level of Foxc2 mRNA is down-regulated whereas hormonal responsiveness increases during differentiation of 3T3-L1 from preadipocytes to adipocytes. At the protein level, immunoblots with Foxc2 antibody demonstrated an induction of Foxc2 by insulin and TNF alpha in nuclear extracts of 3T3-L1 adipocytes. EMSA of nuclear proteins from phorbol-12-myristate-13-acetate- and TNF alpha-treated 3T3-L1 adipocytes using a forkhead consensus oligonucleotide revealed specific binding of a Fox...Continue Reading

Citations

Feb 27, 2009·The Journal of Biological Chemistry·Isabelle GerinOrmond A Macdougald
Jul 18, 2009·Molecular Endocrinology·Ushma R JagFrederick M Stanley
Aug 1, 2014·International Journal of Molecular Sciences·Xiaojuan QuanChunlian Liang
Mar 2, 2016·Journal of Cellular and Molecular Medicine·Chao SunYue Zhou
Dec 17, 2004·Obesity Research·Emma CarlssonMartin Ridderstråle
Jan 29, 2005·Endocrinology·Jérémie BoucherPhilippe Valet

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