Myostatin plays a robust, negative role in controlling muscle mass. A disruption of myostatin function by transgenic expression of its propeptide (the 5′ region, 866 nucleotides) results in significant muscle growth (Yang et al., 2001. Mol Rep Dev 60: 351–361). Studies from myostatin and the propeptide transgene mRNA indicated that myostatin mRNA was detected at day 10.5 postcoitum in fetal mice. Its level remained low, but increased by 180% during the postnatal fast-growth period (day 0–10). An early, high-level postnatal expression of the transgene was identified as being responsible for a highly muscled phenotype. High-fat diet induces adiposity in rodents. To study the effects of dietary fat on muscle growth and adipose tissue fat deposition in the transgenic mice, we challenged the mice with a high-fat diet (45% kcal fat) for 21 weeks. Transgenic mice showed 24%–50% further enhancement of growth on the high-fat diet compared to the normal-fat diet (P= 0.004) from 17 to 25 weeks of age. The total mass of the main muscles of transgenic mice showed a 27% increase on the high-fat diet compared to the normal-fat diet (P= 0.004), while the white adipose tissue mass of the transgenic mice was not significantly different from that of wild-type mice fed a normal-fat diet (P= 0.434). The high-fat diet induced wild-type mice developed 190% greater mass of white adipose tissues compared to the normal-fat diet (P= 0.008), which primarily resulted from enlarged adipocytes. These results demonstrate that disruption of myostatin function by its propeptide shifted dietary fat utilization toward muscle tissues with minimal effects on adiposity. These results suggest that enhancing muscle growth by myostatin propeptide or other means during the early developmental stage may serve as an effective means for obesity prevention. Mol. Reprod. Dev.© 2006 Wiley-Liss, Inc.