Department of Food Hygiene & Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Department of Food Hygiene & Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
J Nutr Biochem. 2021 Sep;95:108762. doi: 10.1016/j.jnutbio.2021.108762. Epub 2021 Jun 5.
The physiological functions of the aryl hydrocarbon receptor (AHR) are only beginning to unfold. Studies in wildtype and AHR knockout (AHRKO) mice have recently disclosed that AHR activity is required for obesity and steatohepatitis to develop when mice are fed with a high-fat diet (HFD). In addition, a line of AHRKO mouse has been reported to accumulate retinoids in the liver. Whether these are universal manifestations across species related to AHR activity level is not known yet. Therefore, we here subjected wildtype and AHRKO male rats (on Sprague-Dawley background) to HFD feeding coupled with free access to 10% sucrose solution and water; controls received a standard diet and water. Although the HFD-fed rats consumed more energy throughout the 24-week feeding regimen, they did not get overweight. However, relative weights of the brown and epididymal adipose tissues were elevated in HFD-fed rats, while that of the liver was lower in AHRKO than wildtype rats. Moreover, the four groups exhibited diet- or genotype-dependent differences in biochemical variables, some of which suggested marked dissimilarities from AHRKO mice. Expression of pro- and anti-inflammatory genes was induced in livers of HFD-fed AHRKO rats, but histologically they did not differ from others. HFD reduced the hepatic concentrations of retinyl palmitate, 9-cis-4-oxo-13,14-dihydroretinoic acid and (suggestively) retinol, whereas AHR status had no effect. Hence, the background strain/line of AHRKO rat is resistant to diet-induced obesity, and AHR does not modulate this or liver retinoid concentrations. Yet, subtle AHR-dependent differences in energy balance-related factors exist despite similar weight development.
芳香烃受体 (AHR) 的生理功能才刚刚开始显现。野生型和 AHR 敲除 (AHRKO) 小鼠的研究最近揭示，当小鼠喂食高脂肪饮食 (HFD) 时，AHR 活性是肥胖和脂肪性肝炎发展所必需的。此外，据报道，AHRKO 小鼠品系在肝脏中积累类视黄醇。这些是否是与 AHR 活性水平相关的物种普遍表现尚不清楚。因此，我们在此将野生型和 AHRKO 雄性大鼠（SD 背景）置于 HFD 喂养，并允许自由摄入 10%蔗糖溶液和水；对照组接受标准饮食和水。尽管 HFD 喂养的大鼠在 24 周的喂养过程中消耗了更多的能量，但它们并没有超重。然而，HFD 喂养的大鼠的棕色和附睾脂肪组织的相对重量增加，而 AHRKO 大鼠的肝脏重量比野生型大鼠低。此外，四组在生化变量方面表现出饮食或基因型依赖性差异，其中一些差异表明与 AHRKO 小鼠明显不同。HFD 喂养的 AHRKO 大鼠肝脏中促炎和抗炎基因的表达被诱导，但组织学上它们与其他组没有区别。HFD 降低了肝脏中棕榈酸视黄酯、9-顺-4-氧代-13,14-二氢视黄酸和（暗示）视黄醇的浓度，而 AHR 状态没有影响。因此，AHRKO 大鼠的背景品系对饮食诱导的肥胖具有抗性，AHR 不会调节这种肥胖或肝脏视黄醇浓度。然而，尽管体重发育相似，仍存在微妙的 AHR 依赖性能量平衡相关因素差异。
