In agreement with this assumption, TSC22D4 expression was significantly reduced in mice fed a high fat diet for 12 weeks, thereby displaying insulin resistance and diet-induced obesity (Supporting Information Fig S2H), overall suggesting that TSC22D4 is downregulated upon metabolic stress conditions, as associated with excess energy stores and availability. Here, TSC22D4 is linked to obesity due to melanocortin 4 receptor deficiency.