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Title: Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
Authors: Gavito, Ana Luisa
Bautista, Dolores
Suarez, Juan
Badran, Samir
Arco, Rocío
Pavón, Francisco Javier
Serrano, Antonia
Rivera, Patricia
Decara, Juan
Cuesta, Antonio Luis
Rodríguez-de-Fonseca, Fernando
Baixeras, Elena
metadata.dc.subject.mesh: Animals
Blood Glucose
Carnitine O-Palmitoyltransferase
Cytokine Receptor gp130
Diet, High-Fat
Fatty Acids
Fatty Liver
Mice, Inbred C57BL
Mice, Obese
Models, Biological
PPAR alpha
Rats, Zucker
Receptors, Leptin
Recombinant Proteins
STAT3 Transcription Factor
Signal Transduction
Suppressor of Cytokine Signaling 3 Protein
Tumor Necrosis Factor-alpha
Issue Date: 22-Jun-2016
Abstract: 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.
metadata.dc.identifier.doi: 10.1371/journal.pone.0157956
Appears in Collections:Producción 2020

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