Journal Article

Obesity Is Mediated by Differential Aryl Hydrocarbon Receptor Signaling in Mice Fed a Western Diet

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

2012

Overview

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 direcdy 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.

• Publisher: National Institute of Environmental Health Sciences,US Department of Health and Human Services
• Subject: Adipose Tissue - metabolism / Animal experimentation / Animals / Aryl hydrocarbon receptors / Biological and medical sciences / Body size / Body Weight / Cardiovascular diseases / Care and treatment / Diet / Dietary Fats - metabolism / Environment. Living conditions / Environmental health / Genes / Genetic aspects / Health aspects / Hydrocarbons / Lipid metabolism / Liver / Liver - metabolism / Medical sciences / Messenger RNA / Metabolic diseases / Mice / Mice, Inbred C57BL / MicroRNA / MicroRNAs - metabolism / Models, Animal / Obesity / Obesity - genetics / Obesity - metabolism / Polymerase Chain Reaction / Public health. Hygiene / Public health. Hygiene-occupational medicine / Receptors / Receptors, Aryl Hydrocarbon - genetics / Receptors, Aryl Hydrocarbon - metabolism / Risk factors / RNA / RNA, Messenger - metabolism / Signal Transduction - drug effects / Toxicants / Toxicology