Given that skeletal muscle expression and circulating levels of Musclin had been positively associated with BMI and seen to be markedly elevated in obese human subjects compared to lean controls (Fig. 1e–h), it was then speculated that the elevation of Musclin in circulation may also impair thermogenic metabolism in human adipose tissues, and thereby playing an essential role in the development of obesity and its associated metabolic defects. This evidence concerns the gene OSTN and obesity due to melanocortin 4 receptor deficiency.