SerpinA3g participates in the antiadipogenesis and insulin-resistance induced by tumor necrosis factor-α in 3T3-F442A cells

Tumor necrosis factor alpha (TNF-alpha) is a proven modulator of adipose metabolism, but the mechanisms by which this cytokine affects the development and function of adipose tissue have not been fully elucidated to date. Using differential display analysis, in this study, we demonstrate that gene expression of the serine protease inhibitor A3g (SerpinA3g) is specifically induced in 3T3-F442A preadipocytes by TNF-alpha but not by other adipogenic inhibitors, such as retinoic acid (RA) or transforming growth factor type beta (TGF-beta). The specific induction of SerpinA3g by TNF-alpha was confirmed by RT-PCR in both preadipose and terminally differentiated 3T3-F442A cells. The knockdown of SerpinA3g using small interfering RNA prevented the antiadipogenesis elicited by TNF-alpha in 3T3-F442A cells but not the antiadipogenesis induced by RA or TGF-beta. SerpinA3g-silenced 3T3-F442A cells also did not display TNF-alpha-induced insulin resistance. Our results demonstrate that SerpinA3g is specifically induced by TNF-a in 3T3-F442A cells, regardless of their stage of differentiation, and participates in the antiadipogenesis and insulin resistance induced by this cytokine. Our results suggest that SerpinA3g plays a role in the TNF-alpha modulation of adipose tissue development and metabolism. Additional studies are warranted regarding the mechanisms mediating adipose SerpinA3g effects. (C) 2014 Elsevier Ltd. All rights reserved.