Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.

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 liv...

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Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17143
Acceso en línea:http://hdl.handle.net/20.500.12105/17143
Access Level:acceso abierto
Palabra clave: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
Animals
Diet, High-Fat
Fatty Liver
Glucose
Humans
Cytokines
Leptin
Lipid Metabolism
Lipids
Lipogenesis
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity
Rats
Rats, Zucker
Receptors, Interleukin-6
Tumor Necrosis Factor-alpha
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/17143
network_acronym_str ES
network_name_str España
repository_id_str
spelling Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.Gavito, Ana LuisaBautista, DoloresSuarez, JuanBadran, SamirArco, RocíoPavón, Francisco-JavierSerrano, AntoniaRivera, PatriciaDecara, JuanCuesta, Antonio LuisRodríguez-de-Fonseca, FernandoBaixeras, ElenaAnimalesAlimentación rica en grasaHígado grasoGlucosaHumanosInterleucina-6LeptinaMetabolismo lipídicoLípidosLipogénesisRatonesRatones consanguíneos C57BLRatones obesosObesidadRatasRatas ZuckerReceptores de interleucina-6Factor de necrosis tumoral alfaAnimalsDiet, High-FatFatty LiverGlucoseHumansCytokinesLeptinLipid MetabolismLipidsLipogenesisMiceMice, Inbred C57BLMice, ObeseObesityRatsRats, ZuckerReceptors, Interleukin-6Tumor Necrosis Factor-alphaHigh-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.Public Library of Science (PLOS)[Gavito,AL; Suarez,J; Arco,J; Pavón,FJ; Serrano,A; Rivera,P; Decara,J; Rodríguez-de-Fonseca,F; Baixera,E] Laboratorio de Investigación, IBIMA, Hospital Regional Universitario de Málaga, Málaga, Spain. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Málaga Spain. [Bautista,D] Unidad de Gestión Clínica de Anatomía Patológica, Hospital Regional Universitario de Málaga, Málaga, Spain. [Pavón,FJ] University College South Denmark, Esbjerg, Denmark. [Cuestya,AL] Danish Diabetes Academy, Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.20242024-01-1620162016-06-2220162016-06-22research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/17143reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/171432026-06-12T12:43:37Z
dc.title.none.fl_str_mv Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
title Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
spellingShingle Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
Gavito, Ana Luisa
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
Animals
Diet, High-Fat
Fatty Liver
Glucose
Humans
Cytokines
Leptin
Lipid Metabolism
Lipids
Lipogenesis
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity
Rats
Rats, Zucker
Receptors, Interleukin-6
Tumor Necrosis Factor-alpha
title_short Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
title_full Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
title_fullStr Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
title_full_unstemmed Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
title_sort Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.
dc.creator.none.fl_str_mv 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
author Gavito, Ana Luisa
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv [Gavito,AL; Suarez,J; Arco,J; Pavón,FJ; Serrano,A; Rivera,P; Decara,J; Rodríguez-de-Fonseca,F; Baixera,E] Laboratorio de Investigación, IBIMA, Hospital Regional Universitario de Málaga, Málaga, Spain. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Málaga Spain. [Bautista,D] Unidad de Gestión Clínica de Anatomía Patológica, Hospital Regional Universitario de Málaga, Málaga, Spain. [Pavón,FJ] University College South Denmark, Esbjerg, Denmark. [Cuestya,AL] Danish Diabetes Academy, Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
dc.subject.none.fl_str_mv 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
Animals
Diet, High-Fat
Fatty Liver
Glucose
Humans
Cytokines
Leptin
Lipid Metabolism
Lipids
Lipogenesis
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity
Rats
Rats, Zucker
Receptors, Interleukin-6
Tumor Necrosis Factor-alpha
topic 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
Animals
Diet, High-Fat
Fatty Liver
Glucose
Humans
Cytokines
Leptin
Lipid Metabolism
Lipids
Lipogenesis
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity
Rats
Rats, Zucker
Receptors, Interleukin-6
Tumor Necrosis Factor-alpha
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-06-22
2016
2016-06-22
2024
2024-01-16
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17143
url http://hdl.handle.net/20.500.12105/17143
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science (PLOS)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425761608269824
score 15.81155

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