title: Aryl hydrocarbon receptor deficiency protects mice from diet-induced adiposity and metabolic disorders through increased energy expenditure.
abstract: OBJECTIVE
  Epidemics of obesity and diabetes are escalating. High-calorie/high-fat food is a major cause for these global health issues, but molecular mechanisms underlying high-fat, diet-induced obesity are still not well understood. The aryl hydrocarbon receptor (AhR), a transcription factor that acts as a xenobiotic sensor, mediates environmental toxicant-induced obesity, insulin resistance and development of diabetes. AhR also influences lipid metabolism and diet-induced obesity. The effects of AhR deficiency on diet-induced obesity, hepatic steatosis and insulin resistance were examined.
  
  
  METHODS
  Male wild-type (WT), AhR null (AhR(-/-)) and AhR heterozygote (AhR(+/-)) mice were fed a normal chow diet (NCD, 10% kcal from fat) or a high-fat diet (HFD, 60% kcal from fat) for up to 14 weeks. Adiposity, adipose and liver morphology, insulin signaling, metabolic parameters and gene profiles were assessed.
  
  
  RESULTS
  AhR deficiency protected against HFD-induced obesity, hepatic steatosis, insulin resistance and inflammation. Moreover, AhR deficiency preserved insulin signaling in major metabolic tissues. These protective effects result from a higher energy expenditure in AhR-deficient mice compared with WT. Levels of transcript for both the thermogenic gene, uncoupling protein 1 (Ucp1), in brown adipose tissue and mitochondrial β-oxidation genes in muscle were significantly higher in AhR(-/-) and AhR(+/-) mice compared with WT.
  
  
  CONCLUSIONS
  This work documents a physiologically relevant function for AhR in regulation of body weight, hepatic fat deposition, insulin sensitivity and energy expenditure under HFD exposure, suggesting that AhR signaling may be developed as a potential therapeutic target for treatment of obesity and metabolic disorders.
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors.forename: Can-Xin
authors.initials: CX
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.|Department of Anesthesiology, Institute of Translation Medicine, the First People's Hospital of Chenzhou, Chenzhou, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors.forename: Cassie D
authors.initials: CD
authors.lastname: Jaeger
authors.affiliation: Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Krager
authors.affiliation: Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Bottum
authors.affiliation: Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha, China.
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Tischkau
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007328:Insulin; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse