Dartmouth-Hitchcock Medical Center, Lebanon, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.
Environ Health Perspect. 2012 Sep;120(9):1252-9. doi: 10.1289/ehp.1205003. Epub 2012 May 18.
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.
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.
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.
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.
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.
肥胖是一个全球性的问题，其原因既有遗传因素，也有环境因素，它是许多疾病的潜在基础。研究表明，毒剂激活的芳香烃受体（AHR）可能会破坏脂肪代谢，导致肥胖。AHR 是一种核受体/转录因子，它最著名的作用是对外源毒物暴露做出反应，从而诱导一系列的外源物质代谢基因。
本研究旨在更直接地测试 AHR 在肥胖和脂肪代谢中的作用，而不是通过外源性毒物。
我们使用了两种在 Ahr 基因上存在差异的同源小鼠模型，这些基因编码的 AHR 信号活性有 10 倍的差异。这两种小鼠品系分别喂食低脂肪（常规）饮食或高脂肪（西式）饮食。
西式饮食对体重、体脂与体重比、肝脏大小和肝脏代谢以及肝脏 mRNA 和 miRNA 谱产生了不同的影响。常规饮食没有显著的差异影响。
这些结果表明，AHR 在肥胖及其相关并发症中发挥着重要作用，并且可能提供了一种简单而有效的治疗策略，以对抗肥胖、心脏病和其他与肥胖相关的疾病。
