Modulation of the effects of a cholesterol-supplemented high-fat diet by aryl hydrocarbon receptor (AHR) activation and/or tryptophan reduction in male mice

This study was conducted to assess the impacts of AHR activation by C2, a potent AHR agonist with low toxicity, and potential AHR inhibition by partial tryptophan (TRP) restriction, on energy balance in male C57BL/6JRccHsd mice. Mice were assigned to one of five feeding groups, control diet (CD), high-fat diet (HFD; 45% of energy from fat), HFD with only 70% of the regular TRP concentration (HFDtrp), HFD supplemented with C2 (HFDc2), or HFDtrp with C2 (HFDtrp-c2). All diets contained 2% cholesterol and were fed for 18 weeks. On weeks 14–16, the mice were tested for gas exchange and locomotor activity, and on weeks 15–17 for glucose tolerance (GTT) and insulin sensitivity (ITT). At termination, tissue samples were collected for biochemical and AI-assisted histological analyses.