TFAM and obesity due to melanocortin 4 receptor deficiency: Our results are supported by previous work showing that knocking out mitochondrial transcription factor TFAM, a key regulator of transcription of mitochondria-encoded genes and of mitochondrial replication and expansion, resulted in the protection of mice from age- and diet-induced obesity, glucose intolerance, and liver steatosis via increased energy expenditure, specifically in adipose tissue53.