By performing detailed metabolic and tissue-level analyses during chronic HFD in Cx3cr1-/- and WT litter mate mice, as well as utilizing hyperinsulinemic euglycemic clamps with tracers to assess whole body and organ specific insulin sensitivity, our studies were designed to detect subtle effects of Cx3cr1 deficiency on the metabolic responses to dietary excess and obesity. This evidence concerns the gene CX3CR1 and obesity due to melanocortin 4 receptor deficiency.