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Int J Obes (Lond). 2015 Aug;39(8):1300-1309. doi: 10.1038/ijo.2015.63. Epub 2015 Apr 24.

Aryl hydrocarbon receptor deficiency protects mice from diet-induced adiposity and metabolic disorders through increased energy expenditure.

Author information

1
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
2
Department of Anesthesiology, Institute of Translation Medicine, the First People's Hospital of Chenzhou, Chenzhou, China.
3
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
4
Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, China.
5
Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha, China.
#
Contributed equally

Abstract

BACKGROUND/OBJECTIVES:

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.

PMID:
25907315
PMCID:
PMC4526411
DOI:
10.1038/ijo.2015.63
[Indexed for MEDLINE]
Free PMC Article

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