Together, our data support that over nutrition renders adipocytes to produce copious amount of Kyn, which then exacerbates insulin resistance via the AhR/STAT3/IL-6 axis, and therefore, supplementation of Vit-B6 enhanced Kyn catabolism and protected mice from HFD-induced obesity and insulin resistance. This evidence concerns the gene STAT3 and obesity due to melanocortin 4 receptor deficiency.