LEP and obesity due to melanocortin 4 receptor deficiency: TIMP2−/− mice were found hyperphagic before the onset of obesity and were leptin resistant as evidenced by reduced leptin signaling in the arcuate nucleus of 2 month-old TIMP2−/− mice fed a chow diet compared to control mice as well as decreased response to leptin administration on food consumption, as evidenced by decreased leptin-mediated STAT3 activation [171].