2026-06-14T04:02:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/188782024-11-28T14:51:43Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Vida, Margarita
author
Gavito, Ana Luisa
author
Pavón, Francisco-Javier
author
Bautista, Dolores
author
Serrano, Antonia
author
Suarez, Juan
author
Arrabal, Sergio
author
Decara, Juan
author
Romero-Cuevas, Miguel
author
Rodríguez De Fonseca, Fernando
author
Baixeras, Elena
authoraffiliation
[Vida,M; Gavito,AL; Pavón,FJ; Serrano,A; Suarez,J; Arrabal,S; Decara,J; Romero-Cuevas,M; Rodríguez de Fonseca,F; Baixeras,E] Laboratorio de Investigacioón, IBIMA/Universidad de Málaga, Málaga, Spain. [Vida,M; Gavito,AL; Pavón,FJ; Serrano,A; Suarez
2024-03-05T07:38:58Z
2024-03-05T07:38:58Z
2015-07-01
10.1242/dmm.019166
1754-8411
1754-8403
Disease Models & Mechanisms
http://hdl.handle.net/10668/2233
26035386
http://hdl.handle.net/20.500.12105/18878
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 (ACC?/?), 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 ACC?/?, 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.
eng
Interleukin-6
Liver
Lipogenesis
Steatosis
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice
research article