2026-07-21T13:51:00Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/176102024-09-21T19:11:28Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Decara, Juan author Serrano, Antonia author Pavón, Francisco Javier author Rivera, Patricia author Arco, Rocio author Gavito, Ana author Vargas, Antonio author Navarro, Juan A author Tovar, Ruben author Lopez-Gambero, Antonio J author Suárez, Juan author Rodríguez de Fonseca, Fernando author Baixeras, Elena 2024-02-08T14:41:33Z 2024-02-08T14:41:33Z 2018-06-29 10.1038/s41598-018-27871-7 2045-2322 Scientific reports http://hdl.handle.net/10668/12661 29959379 http://hdl.handle.net/20.500.12105/17610 Chronic NP-1 administration reduces body weight and hepatic steatosis despite induction of tolerance in adiponectin gene transcription with respect to the acute actions of this drug. This study explored the hypothesis that NP-1 could exert these effects through mechanisms independent of adiponectin. To this aim, we took advantage of the Zucker (fa/fa) rat model, which exhibits obesity, fatty liver and elevated leptin and adiponectin levels. Body weight and food intake were reduced after chronic NP-1 treatment. Plasma TNFα concentrations were elevated but no increase in adiponectin was found. Even so, NP-1 ameliorated fatty liver and corrected dyslipidemia by mechanisms probably associated with reduced feeding, transcription of Cpt1 and down-regulation of Hmgcr-CoA expression. In brown fat tissue NP-1 increased Dnmt1 (inhibitor of Adipoq) while it reduced Ucp1 expression and heat production, which excludes thermogenesis as a mechanism of the NP-1 slimming effect. The anti-obesity action of chronic NP-1 administration might be mediated by TNFα, which is known to have anorectic actions in the hypothalamus and to regulate both Dmnt1 and Ucp1 expression in adipose tissues. This finding opens up the possibility of using NP-1-mediated TNFα-induced weight loss as an innovative treatment of complicated obesity under strict pharmacologic control. eng The adiponectin promoter activator NP-1 induces high levels of circulating TNFα and weight loss in obese (fa/fa) Zucker rats. research article