NRGN and obesity due to melanocortin 4 receptor deficiency: Here, we questioned whether Ng+/- mice fed a high-fat diet (HFD) to induce obesity, which is a condition that necessitates SERCA mediated Ca2+ cycling, would have lower SERCA efficiency in muscle due to enhanced calcineurin signaling and the promotion of SLN expression and, in turn, a better metabolic phenotype of lower body mass, body fat, and improved insulin and glucose tolerance.