For instance, genetic disruption of IL-4/13 signaling or eosinophils impairs cold-inducible beige adipocytes, and conversely, administration of IL-4 increases beige adipocytes to recover obesity in thermoneutral mice; that is, eosinophils and type 2 cytokine signaling in macrophages require thermogenic activation [73]. This evidence concerns the gene IL4 and obesity due to melanocortin 4 receptor deficiency.