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oai:repisalud.isciii.es:20.500.12105/171432024-11-28T15:00:41Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Gavito, Ana Luisa author Bautista, Dolores author Suarez, Juan author Badran, Samir author Arco, Rocío author Pavón, Francisco-Javier author Serrano, Antonia author Rivera, Patricia author Decara, Juan author Cuesta, Antonio Luis author Rodríguez-de-Fonseca, Fernando author Baixeras, Elena author 2016-06-22 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. 10.1371/journal.pone.0157956 1932-6203 PloS One http://hdl.handle.net/10668/2399 27333268 http://hdl.handle.net/20.500.12105/17143 Animales Alimentación rica en grasa Hígado graso Glucosa Humanos Interleucina-6 Leptina Metabolismo lipídico Lípidos Lipogénesis Ratones Ratones consanguíneos C57BL Ratones obesos Obesidad Ratas Ratas Zucker Receptores de interleucina-6 Factor de necrosis tumoral alfa Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.