Here, we investigate the effects of MGAT2 inhibition on (a) fat‐induced gut peptide release and fat intake in normal mice and (b) metabolic disorders in ob/ob mice fed on a high‐fat diet, a model of severe obesity and type 2 diabetes, using a selective MGAT2 inhibitor. This evidence concerns the gene MGAT2 and obesity due to melanocortin 4 receptor deficiency.