title: TNFα gene knockout differentially affects lipid deposition in liver and skeletal muscle of high-fat-diet mice.
abstract: OBJECTIVE
  Inflammation and ectopic lipid deposition contribute to obesity-related insulin resistance (IR). Studies have shown that deficiency of the proinflammatory cytokine tumor necrosis factor-α (TNFα) protects against the IR induced by a high-fat diet (HFD). We aimed to evaluate the relationship between HFD-related inflammation and lipid deposition in skeletal muscle and liver.
  
  
  METHODS
  Wild-type (WT) and TNFα-deficient (TNFα-KO) mice were subjected to an HFD for 12 weeks. A glucose tolerance test was performed to evaluate IR. Inflammatory status was assessed by measuring plasma and tissue transcript levels of cytokines. Lipid intermediate concentrations were measured in plasma, muscle and liver. The expression of genes involved in fatty acid transport, synthesis and oxidation was analyzed in adipose tissue, muscle and liver.
  
  
  RESULTS
  HFD induced a higher body weight gain in TNFα-KO mice than in WT mice. The weight of epididymal and abdominal adipose tissues was twofold lower in WT mice than in TNFα-KO mice, whereas liver weight was significantly heavier in WT mice. IR, systemic and adipose tissue inflammation, and plasma nonesterified fatty acid levels were reduced in TNFα-KO mice fed an HFD. TNFα deficiency improved fatty acid metabolism and had a protective effect against lipid deposition, inflammation and fibrosis associated with HFD in liver but had no impact on these markers in muscle.
  
  
  CONCLUSIONS
  Our data suggest that in an HFD context, TNFα deficiency reduced hepatic lipid accumulation through two mechanisms: an increase in adipose tissue storage capacity and a decrease in fatty acid uptake and synthesis in the liver.
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Salles
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tardif
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Landrier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mothe-Satney
authors.forename: Christelle
authors.initials: C
authors.lastname: Guillet
authors.forename: Carole
authors.initials: C
authors.lastname: Boue-Vaysse
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
authors.forename: Christophe
authors.initials: C
authors.lastname: Giraudet
authors.forename: Véronique
authors.initials: V
authors.lastname: Patrac
authors.forename: Justine
authors.initials: J
authors.lastname: Bertrand-Michel
authors.forename: Philippe
authors.initials: P
authors.lastname: Denis
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chardigny
authors.forename: Yves
authors.initials: Y
authors.lastname: Boirie
authors.forename: Stéphane
authors.initials: S
authors.lastname: Walrand
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002518:Ceramides / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D002518:Ceramides; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D014409:Tumor Necrosis Factor-alpha