Abstract
In spite of their shared decrease of insulin resistance, oleoyl-estrone [OE], and rosiglitazone show diverging effects on body fat mass and distribution. In this study, we studied whether their effects on white adipose tissue [WAT] were due to a shared or synergistic mechanism of action. Combined effects of OE and rosiglitazone 10-day treatment on WAT lipid, cell mass/number, and the expression of key lipid metabolism and regulatory agents were studied using an adult male overweight rat model. OE decreased WAT cell mass and lipids, parameters not changed by rosiglitazone. The effects of OE and—specially—rosiglitazone were more marked in small-cell WAT (i.e., mesenteric and subcutaneous sites) than in larger cell WAT (retroperitoneal and perigonadal). OE decreased the expressions in WAT of lipogenic enzymes, lipoprotein lipase, PPARs, and SREBP1c, effects symmetrically reversed by rosiglitazone. OE showed no effects on hormone-sensitive lipase expression, which was increased by rosiglitazone. OE strongly inhibited WAT lipogenesis, leaving lipolysis unchanged, thus unbalancing (and helping mobilize) WAT lipid stores. Rosiglitazone acted practically only on small-cell WAT sites, where it favored lipogenesis, but also stimulated lipolysis, which resulted in limited changes in lipid stores. Combination of OE and rosiglitazone induced less fat loss than OE alone.
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The financial and material help for the development of this study of OED S.L. and CIBER Obesidad y Nutrición, Instituto de Salud Carlos III, as well as grants PI052179 of the Fondo de Investigaciones Sanitarias and SAF2006-05134 of the Plan Nacional de Investigación en Biomedicina of Spain, are gratefully acknowledged.
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Ferrer-Lorente, R., Cabot, C., Fernández-López, J.A. et al. Site-specific modulation of white adipose tissue lipid metabolism by oleoyl-estrone and/or rosiglitazone in overweight rats. Naunyn-Schmied Arch Pharmacol 381, 339–348 (2010). https://doi.org/10.1007/s00210-010-0495-8
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DOI: https://doi.org/10.1007/s00210-010-0495-8