The fat-specific loss of glycine amidinotransferase (GATM), which is the rate-limiting enzyme for creatine biosynthesis, exhibited cold intolerance and low creatine levels and promoted diet-induced obesity due to the repression of energy expenditure that was induced in response to high-calorie feeding [128]. The gene discussed is GATM; the disease is obesity due to melanocortin 4 receptor deficiency.