TBC1D1 and obesity due to melanocortin 4 receptor deficiency: For instance, both human and mouse studies link a bona fide AMPK substrate TBC1D1 to the development of obesity.233,234 Wang and Chen groups introduced a knockin mutation that prevents the phosphorylation of TBC1D1 by activated AMPK and found that the knockin mice developed obesity on a normal chow diet.