Between lean and obese animals by quantifying myostatin and ActRIIB gene and protein expression in skeletal muscle and adipose tissue, and measuring serum myostatin concentrations. This study presents preliminary data which provide the first indication of a possible association between BCS and myostatin gene expression and secretion in horses and ponies. The increased gene expression of myostatin in skeletal muscles of obese animals is in agreement with similar data for mice where myostatin mRNA levels were significantly greater in tibialis anterior muscle in ob/ob mice compared to wild-type mice. In that study, the expression of ActRIIB was not different between lean and obese animals for skeletal muscle, whereas in the current study, ActRIIB mRNA was significantly down-regulated in three out of the four skeletal muscles studied. This may be suggestive of some element of negative feedback Dabrafenib regulation between myostatin and ActRIIB. Increased expression of myostatin protein has been identified in the vastus lateralis muscle from extremely obese human subjects. Perhaps the lack of statistical significance observed in the current study may be due to absolute differences in body fat content between species. Obese horses and ponies were found to have up to 30% body fat recorded in a previous study, which is considerably lower than the body fat content of morbidly obese humans which was found to average 48.5%. The finding of altered myostatin and ActRIIB mRNA expression in muscle without parallel changes in protein expression has previously been shown. It is known that the mRNA expression of a particular gene is not always predictive of protein expression, and the correlation between the two can vary significantly. There are several possible explanations for the differences between the gene and protein expression including variation in protein half-lives, complex post-transcriptional mechanisms, and different sensitivities in methodologies for detecting mRNA and protein expressions. Circulating concentrations of myostatin were significantly higher in obese than in lean animals in the current study. This is consistent with previous observations of increased myostatin secretion from myotubes derived from muscle of extremely obese humans. In the current study there was one clear outlier in our lean group of animals for both circulating concentrations and mRNA expression of myostatin which upon investigation was found to be the Welsh pony mare. It could be speculated that this may be indicative of an increased propensity towards obesity based on a finding from a murine study in which obesity-susceptible strain of mice had increased mRNA expression of myostatin in skeletal muscle compared to an obesityresistant strain of mice, SWR/J. Myostatin gene expression was generally low in adipose tissues but was significantly higher in crest fat from obese than lean animals. Increased fat deposition in this subcutaneous fat depot along the nuchal crest of the neck in horses and ponies has been associated with laminitis risk, hyperinsulinemia, and has been proposed to be an important source of proinflammatory cytokines. Differences in myostatin gene expression between crest fat samples from lean and obese animals were not reflected in protein expression in this tissue.