Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a western diet

Joanna S. Kerley-Hamilton, Heidi W. Trask, Christian J.A. Ridley, Eric Dufour, Carol S. Ringelberg, Nilufer Nurinova, Diandra Wong, Karen L. Moodie, Samantha L. Shipman, Jason H. Moore, Murray Korc, Nicholas W. Shworak, Craig R. Tomlinson

Research output: Contribution to journalArticle

44 Scopus citations

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. Objectives: 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.

Original languageEnglish (US)
Pages (from-to)1252-1259
Number of pages8
JournalEnvironmental Health Perspectives
Volume120
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Aryl hydrocarbon receptor
  • Gene-environment interaction
  • Liver
  • Obesity
  • Western diet
  • mRNA
  • miRNA

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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    Kerley-Hamilton, J. S., Trask, H. W., Ridley, C. J. A., Dufour, E., Ringelberg, C. S., Nurinova, N., Wong, D., Moodie, K. L., Shipman, S. L., Moore, J. H., Korc, M., Shworak, N. W., & Tomlinson, C. R. (2012). Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a western diet. Environmental Health Perspectives, 120(9), 1252-1259. https://doi.org/10.1289/ehp.1205003