title: Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice.
abstract: OBJECTIVE
  Lipogenesis is intimately controlled by hormones and cytokines as well as nutritional conditions. IL-6 participates in the regulation of fatty acid metabolism in the liver. We investigated the role of IL-6 in mediating fasting/re-feeding changes in the expression of hepatic lipogenic enzymes.
  
  
  METHODS
  Gene and protein expression of lipogenic enzymes were examined in livers of wild-type (WT) and IL-6-deficient (IL-6(-/-) ) mice during fasting and re-feeding conditions. Effects of exogenous IL-6 administration on gene expression of these enzymes were evaluated in vivo. The involvement of STAT3 in mediating these IL-6 responses was investigated by using siRNA in human HepG2 cells.
  
  
  RESULTS
  During feeding, the up-regulation in the hepatic expression of lipogenic genes presented similar time kinetics in WT and IL-6(-/-) mice. During fasting, expression of lipogenic genes decreased gradually over time in both strains, although the initial drop was more marked in IL-6(-/-) mice. Protein levels of hepatic lipogenic enzymes were lower in IL-6(-/-) than in WT mice at the end of the fasting period. In WT, circulating IL-6 levels paralleled gene expression of hepatic lipogenic enzymes. IL-6 administration in vivo and in vitro showed that IL-6-mediated signalling was associated with the up-regulation of hepatic lipogenic enzyme genes. Moreover, silencing STAT3 in HepG2 cells attenuated IL-6 mediated up-regulation of lipogenic gene transcription levels.
  
  
  CONCLUSIONS
  IL-6 sustains levels of hepatic lipogenic enzymes during fasting through activation of STAT3. Our findings indicate that clinical use of STAT3-associated signalling cytokines, particularly against steatosis, should be undertaken with caution.
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: A L
authors.initials: AL
authors.lastname: Gavito
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Cabello
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Suarez
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Serrano
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Pavón
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Vida
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Romero
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC/UAM), Madrid, 28029, Spain.|Ciber de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, 28029, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Pardo
authors.affiliation: Unidad de Gestión Clínica de Anatomía Patológica, Hospital Regional Universitario de Málaga, Málaga 29010, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Bautista
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Arrabal
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Decara
authors.affiliation: Danish Diabetes Academy, Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A L
authors.initials: AL
authors.lastname: Cuesta
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC/UAM), Madrid, 28029, Spain.|Ciber de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, 28029, Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: Valverde
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Málaga, 29010, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain.|UGC-Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Baixeras
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005215:Fasting / Q000378:metabolism*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D054890:Fatty Acid Synthase, Type I; C498191:Acacb protein, mouse; D000103:Acetyl-CoA Carboxylase