%0 Journal Article
%A Gavito, Ana Luisa
%A Bautista, Dolores
%A Suarez, Juan
%A Badran, Samir
%A Arco, Rocío
%A Pavón, Francisco Javier
%A Serrano, Antonia
%A Rivera, Patricia
%A Decara, Juan
%A Cuesta, Antonio Luis
%A Rodríguez-de-Fonseca, Fernando
%A Baixeras, Elena
%T Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
%D 2016
%U http://hdl.handle.net/10668/2399
%X High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats.
%K Animales
%K Alimentación rica en grasa
%K Hígado graso
%K Glucosa
%K Humanos
%K Interleucina-6
%K Leptina
%K Metabolismo lipídico
%K Lípidos
%K Lipogénesis
%K Ratones
%K Ratones consanguíneos C57BL
%K Ratones obesos
%K Obesidad
%K Ratas
%K Ratas Zucker
%K Receptores de interleucina-6
%K Factor de necrosis tumoral alfa
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