Abstract
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.
Highlights
The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) was originally discovered as the mediator of xenobiotic-metabolizing enzyme induction by, and toxicity of, both polycyclic aromatic hydrocarbons and dioxin-like polyhalogenated compounds [1]
Whereas the rats fed with standard diet (SD) had only water to drink, those fed with high-fat diet (HFD) could freely select between water and 10% sucrose solution, up to the point that they reached the weight of 600 g
This manifested itself as a steady rise in the contribution of sucrose to the total energy intake, reaching an equal level to the diet by 21 weeks (Supplementary Fig. S1). This change was evident as a highly significant (P
Summary
The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) was originally discovered as the mediator of xenobiotic-metabolizing enzyme induction by, and toxicity of, both polycyclic aromatic hydrocarbons and dioxin-like polyhalogenated compounds [1]. More recent studies have primarily focussed on its numerous physiological roles. Much research has been devoted to AHR’s critical participation in the maintenance of intestinal microbiome stability and mucosal integrity [9,10,11,12,13]. A novel action of the AHR, possibly related to its intestinal impacts, came to light a few years ago.
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