title: C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet.
abstract: OBJECTIVE
  Inflammation is associated with obesity and has been implicated in the development of diabetes and atherosclerosis. During gram-negative bacterial infection, lipopolysaccharide causes an inflammatory reaction via toll-like receptor 4 (TLR4), which has an essential function in the induction of innate and adaptative immunity. Our aim was to determine what role TLR4 plays in the development of metabolic phenotypes during high-fat feeding.
  
  
  METHODS
  We evaluated metabolic consequences of a high-fat diet in TLR4 mutant mice (C3H/HeJ) and their respective controls.
  
  
  RESULTS
  TLR4 inactivation reduced food intake without significant modification of body weight, but with higher epididymal adipose tissue mass and adipocyte hypertrophy. It also attenuated the inflammatory response and increased glucose transport and the expression levels of adiponectin and lipogenic markers in white adipose tissue. In addition, TLR4 inactivation blunted insulin resistance induced by lipopolysaccharide in differentiated adipocytes. Increased feeding efficiency in TLR4 mutant mice was associated with lower mass and lower expression of uncoupling protein 1 gene in brown adipose tissue. Finally, TLR4 inactivation slowed the development of hepatic steatosis, reducing the liver triacylglycerol content and also expression levels of lipogenic and fibrosis markers.
  
  
  CONCLUSIONS
  TLR4 influences white adipose tissue inflammation and insulin sensitivity, as well as liver fat storage, and is important in the regulation of metabolic phenotype during a fat-enriched diet.
authors.affiliation: INSERM UMR 626; Faculté de Médecine Timone, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: M
authors.initials: M
authors.lastname: Poggi
authors.forename: D
authors.initials: D
authors.lastname: Bastelica
authors.forename: P
authors.initials: P
authors.lastname: Gual
authors.forename: M A
authors.initials: MA
authors.lastname: Iglesias
authors.forename: T
authors.initials: T
authors.lastname: Gremeaux
authors.forename: C
authors.initials: C
authors.lastname: Knauf
authors.forename: F
authors.initials: F
authors.lastname: Peiretti
authors.forename: M
authors.initials: M
authors.lastname: Verdier
authors.forename: I
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: J F
authors.initials: JF
authors.lastname: Tanti
authors.forename: R
authors.initials: R
authors.lastname: Burcelin
authors.forename: M C
authors.initials: MC
authors.lastname: Alessi
mesh_terms: D000273:Adipose Tissue / Q000502:physiology* / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D006019:Glycolysis; D007249:Inflammation; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation; D016133:Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D008055:Lipids; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014280:Triglycerides