title: Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a Western diet.
abstract: BACKGROUND
  Obesity is a growing worldwide problem with genetic and environmental causes, and it is an underlying basis for many diseases. Studies have shown that the toxicant-activated aryl hydrocarbon receptor (AHR) may disrupt fat metabolism and contribute to obesity. The AHR is a nuclear receptor/transcription factor that is best known for responding to environmental toxicant exposures to induce a battery of xenobiotic-metabolizing genes.
  
  
  OBJECTIVE
  The intent of the work reported here was to test more directly the role of the AHR in obesity and fat metabolism in lieu of exogenous toxicants.
  
  
  METHODS
  We used two congenic mouse models that differ at the Ahr gene and encode AHRs with a 10-fold difference in signaling activity. The two mouse strains were fed either a low-fat (regular) diet or a high-fat (Western) diet.
  
  
  RESULTS
  The Western diet differentially affected body size, body fat:body mass ratios, liver size and liver metabolism, and liver mRNA and miRNA profiles. The regular diet had no significant differential effects.
  
  
  CONCLUSIONS
  The results suggest that the AHR plays a large and broad role in obesity and associated complications, and importantly, may provide a simple and effective therapeutic strategy to combat obesity, heart disease, and other obesity-associated illnesses.
authors.affiliation: Dartmouth-Hitchcock Medical Center, Lebanon, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Kerley-Hamilton
authors.forename: Heidi W
authors.initials: HW
authors.lastname: Trask
authors.forename: Christian J A
authors.initials: CJ
authors.lastname: Ridley
authors.forename: Eric
authors.initials: E
authors.lastname: Dufour
authors.forename: Carol S
authors.initials: CS
authors.lastname: Ringelberg
authors.forename: Nilufer
authors.initials: N
authors.lastname: Nurinova
authors.forename: Diandra
authors.initials: D
authors.lastname: Wong
authors.forename: Karen L
authors.initials: KL
authors.lastname: Moodie
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Shipman
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Shworak
authors.forename: Craig R
authors.initials: CR
authors.lastname: Tomlinson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D023421:Models, Animal; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D035683:MicroRNAs; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon