The increasing prevalence of metabolic diseases is a characteristic of industrialized countries and may be linked to the enhanced uptake of anthropogenic chemicals from the environment. In this project, we investigate the influence of the aryl hydrocarbon receptor (AhR) and the AhR repressor (AhRR) on macrophage (MΦ) programming in metaflammation. The activation of the AhR through environmental toxins was shown to promote obesity, whereas phytochemicals – that naturally occur in vegetables - also bind to the AhR and exert protective effects. We showed that myeloid cells respond to AhR stimulation by expression of the AhRR and that AhRR-deficient mice are protected from diet-induced obesity (DIO). We propose to investigate the function of the AhRR in metaflammation with a focus on transcriptional and metabolic programming of MΦ. Further, the direct consequences of AhR activation by the environmental toxin3-methylcholanthrene (3-MC), the phytochemical indolocarbazole (ICZ), and the plasticizerbisphenol-A (BpA) on MΦ programming will be examined. By a combined analysis of transcriptomic and metabolomic data, we aim to unravel the mode of action of the AhR/AhRR in myeloid cells in the regulation of metaflammation.