A recent study reported that CARD9−/− mice had significantly decreased numbers of infiltrating macrophages in the heart, which prevented myocardial dysfunction and ameliorated high fat diet-induced insulin resistance and glucose intolerance, leading to alleviation of high fat diet-induced obesity potentially through CARD9-dependent p38 suppression90. Here, CARD9 is linked to obesity due to melanocortin 4 receptor deficiency.