title: TNF and IL-18 cytokines may regulate liver fat storage under homeostasis conditions.
abstract: The inflammation induced by obesogenic diets is associated with deposition of fat in the liver. On the other hand, anti-inflammatory and immunosuppressive therapies may impact in body fat storage and in liver lipid dynamics. It is important to study specific inflammatory mediators in this context, since their role on hepatic damage is not fully clarified. This study aimed to evaluate the role of interleukin (IL)-18 and tumor necrosis factor (TNF) receptor in liver dysfunction induced by diet. Male C57BL/6 wild-type (WT), IL-18, and TNF receptor 1 knockout mice (IL-18-/-and TNFR1-/-) were divided according to the experimental diets: chow diet or a high-refined carbohydrate-containing diet. Alanine aminotransferase was quantified by colorimetric analysis. Total fat content in the liver was determined by Folch methods. Levels of TNF, IL-6, IL-4, and IL-13 in liver samples were measured by ELISA assay. IL-18 and TNFR knockout mice fed with chow diet showed higher liver triglycerides deposition than WT mice fed with the same diet (WT: 131.9 ± 24.5; IL-18-/-: 239.4 ± 38.12*; TNF-/-: 179.6 ± 50.45*; *P < 0.01). Furthermore, these animals also showed a worse liver histopathological score and lower levels of TNF, IL-6, IL-4, and IL-13 in the liver. Interestingly, treatment with a high-carbohydrate diet did not exacerbate liver damage in IL-18-/-and TNFR1-/-mice. Our data suggest that IL-18 and TNF may be involved on hepatic homeostasis mainly in a context of a healthy diet.
authors.affiliation: a Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|b Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Jaqueline Pereira
authors.initials: JP
authors.lastname: Lana
authors.affiliation: a Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|b Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Laís Bhering
authors.initials: LB
authors.lastname: Martins
authors.affiliation: a Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|b Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marina Chaves de
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: b Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Zélia
authors.initials: Z
authors.lastname: Menezes-Garcia
authors.affiliation: c Faculty of Nutrition, Universidade Federal de Alfenas, Alfenas, Brazil.
authors.forename: Letícia Tamie Pavia
authors.initials: LT
authors.lastname: Yamada
authors.affiliation: b Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Leda Quercia
authors.initials: LQ
authors.lastname: Vieira
authors.affiliation: b Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: a Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|b Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Adaliene Versiani Matos
authors.initials: AV
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D000070601:Diet, Carbohydrate Loading / Q000009:adverse effects; D005511:Food Handling; D058847:Inflammasomes / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D058847:Inflammasomes; D018793:Interleukin-13; D020382:Interleukin-18; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D015847:Interleukin-4; D003094:Collagen
keywords: dysfonction métabolique; foie; high refined carbohydrate-containing diet; inflammation; interleukin-18; interleukine-18; liver; metabolic dysfunction; récepteur 1 du facteur de nécrose tumorale; régime riche en sucres hautement raffinés; tumor necrosis factor receptor 1