Animals that lack Letmd1 have abnormal BAT morphology (Figures 3A, 3F, and 3K) and dramatically reduced ability to produce heat (Figures 2C-2G), as well as a predisposition to diet-induced obesity and impaired glucose disposal (Figures 2H-2K). Here, LETMD1 is linked to obesity due to melanocortin 4 receptor deficiency.