title: SerpinA3g participates in the antiadipogenesis and insulin-resistance induced by tumor necrosis factor-α in 3T3-F442A cells.
abstract: Tumor necrosis factor alpha (TNF-α) 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-α but not by other adipogenic inhibitors, such as retinoic acid (RA) or transforming growth factor type beta (TGF-β). The specific induction of SerpinA3g by TNF-α 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-α in 3T3-F442A cells but not the antiadipogenesis induced by RA or TGF-β. SerpinA3g-silenced 3T3-F442A cells also did not display TNF-α-induced insulin resistance. Our results demonstrate that SerpinA3g is specifically induced by TNF-α 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-α modulation of adipose tissue development and metabolism. Additional studies are warranted regarding the mechanisms mediating adipose SerpinA3g effects.
authors: Instituto Potosino de Investigación Científica y Tecnológica, Molecular Biology Division, San Luis Potosí, México. Electronic address: olivo@ipicyt.edu.mx.
authors: Luis A
authors: LA
authors: Salazar-Olivo
authors: Instituto Potosino de Investigación Científica y Tecnológica, Molecular Biology Division, San Luis Potosí, México.
authors: Rebeca
authors: R
authors: Mejia-Elizondo
authors: Instituto Potosino de Investigación Científica y Tecnológica, Molecular Biology Division, San Luis Potosí, México.
authors: Angel Josabad
authors: AJ
authors: Alonso-Castro
authors: Universidad de Guanajuato, Department of Biology, Division of Natural and Exact Sciences, Guanajuato, México.
authors: Patricia
authors: P
authors: Ponce-Noyola
authors: Instituto Nacional de Medicina Genómica, México DF, México.
authors: Vilma
authors: V
authors: Maldonado-Lagunas
authors: Instituto Nacional de Medicina Genómica, México DF, México.
authors: Jorge
authors: J
authors: Melendez-Zajgla
authors: Universidad Autónoma de San Luis Potosí, Faculty of Medicine, San Luis Potosí, México.
authors: Victor Mateo
authors: VM
authors: Saavedra-Alanis
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001483:Base Sequence; D007333:Insulin Resistance; D051379:Mice; D008969:Molecular Sequence Data; D015843:Serpins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C490400:Serpina3k protein, mouse; D015843:Serpins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin
keywords: 3T3 adipogenesis; Insulin resistance; SerpinA3g; TNF-α; siRNA