RT Journal Article
T1 Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice.
A1 Vida, Margarita
A1 Gavito, Ana Luisa
A1 Pavón, Francisco Javier
A1 Bautista, Dolores
A1 Serrano, Antonia
A1 Suarez, Juan
A1 Arrabal, Sergio
A1 Decara, Juan
A1 Romero-Cuevas, Miguel
A1 Rodríguez de Fonseca, Fernando
A1 Baixeras, Elena
K1 Liver
K1 Lipogenesis
K1 Steatosis
K1 Interleukin-6
K1 Modelos de enfermedad en animales
K1 Ácido graso sintasa tipo I
K1 Células Hep G2
K1 Interleucina-6
K1 Lipogénesis
K1 Hígado
K1 Ratones
K1 Ratones consanguíneos C57BL
K1 Ratones noqueados
K1 Esteatosis hepática no alcohólica
K1 Fosforilación
K1 Proteínas recombinantes
K1 Factor de transcripción STAT3
K1 Estearoil-CoA desaturasa
K1 Supresor de proteínas señalizadoras de citocinas
K1 Citoquinesis
K1 Carnitina O-palmitoiltransferasa
K1 Acetil-CoA carboxilasa
K1 Alimentación rica en grasa
AB Interleukin-6 (IL-6) has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD) in wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice. Additionally, HFD-fed IL-6(-/-) mice were also chronically treated with recombinant IL-6 (rIL-6). Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1) and signal transducer and activator of transcription-3 (STAT3), increased AMP kinase phosphorylation (p-AMPK), and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). The HFD-fed IL-6(-/-) mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β), FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6 -/-: mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.
PB Company of Biologists
SN 1754-8403
YR 2015
FD 2015-07-01
LK http://hdl.handle.net/10668/2233
UL http://hdl.handle.net/10668/2233
LA en
NO Vida M, Gavito AL, Pavón FJ, Bautista D, Serrano A, Suarez J, et al. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice. Dis Model Mech. 2015                         ; 8(7):721-31
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025