Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice
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...
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The Company of Biologists
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doaj-0a74cc0a9e8240e0bde5b059af78fbdc2020-11-25T00:06:33ZengThe Company of BiologistsDisease Models & Mechanisms1754-84111754-84032015-07-018772173110.1242/dmm.019166019166Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient miceMargarita Vida0Ana Luisa Gavito1Francisco Javier Pavón2Dolores Bautista3Antonia Serrano4Juan Suarez5Sergio Arrabal6Juan Decara7Miguel Romero-Cuevas8Fernando Rodríguez de Fonseca9Elena Baixeras10 Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Unidad de Gestión Clínica de Anatomía Patológica, Hospital Universitario Regional de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain Laboratorio de Investigación, IBIMA/Universidad de Málaga, 29010 Málaga, Spain 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.http://dmm.biologists.org/content/8/7/721Interleukin-6LiverLipogenesisSteatosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Margarita Vida Ana Luisa Gavito Francisco Javier Pavón Dolores Bautista Antonia Serrano Juan Suarez Sergio Arrabal Juan Decara Miguel Romero-Cuevas Fernando Rodríguez de Fonseca Elena Baixeras |
spellingShingle |
Margarita Vida Ana Luisa Gavito Francisco Javier Pavón Dolores Bautista Antonia Serrano Juan Suarez Sergio Arrabal Juan Decara Miguel Romero-Cuevas Fernando Rodríguez de Fonseca Elena Baixeras Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice Disease Models & Mechanisms Interleukin-6 Liver Lipogenesis Steatosis |
author_facet |
Margarita Vida Ana Luisa Gavito Francisco Javier Pavón Dolores Bautista Antonia Serrano Juan Suarez Sergio Arrabal Juan Decara Miguel Romero-Cuevas Fernando Rodríguez de Fonseca Elena Baixeras |
author_sort |
Margarita Vida |
title |
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice |
title_short |
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice |
title_full |
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice |
title_fullStr |
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice |
title_full_unstemmed |
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice |
title_sort |
chronic administration of recombinant il-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in il-6-deficient mice |
publisher |
The Company of Biologists |
series |
Disease Models & Mechanisms |
issn |
1754-8411 1754-8403 |
publishDate |
2015-07-01 |
description |
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. |
topic |
Interleukin-6 Liver Lipogenesis Steatosis |
url |
http://dmm.biologists.org/content/8/7/721 |
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