No abstract

In mice, the myostatin (Mstn) null mutation and treatment with clenbuterol both increase muscle growth and decrease fat mass. Our objective was to determine whether mechanistic overlap exists by administering clenbuterol to Mstn null mice. Male Mstn null and wild-type mice of similar genetic backgrounds received either 0 (control) or 20 p.p.m. clenbuterol in tap water free choice for 14 days. Several traits were measured to estimate muscle and fat growth. The Mstn null mutation resulted in increased body and empty carcass weight, increased muscle weights and decreased fat pad weights. Fat content was reduced and protein content was increased in the empty carcasses of Mstn null mice. Similarly, treatment with clenbuterol resulted in increased body and empty carcass weight, increased muscle weights and reduced fat pad weights. Fat content of empty carcasses and viscera was reduced and protein content of empty carcasses was increased with clenbuterol treatment. A significant interaction of genotype and clenbuterol treatment would indicate an altered responsiveness of Mstn null mice to clenbuterol. However, only the weight of gastrocnemius muscles exhibited a significant (P 5 0.01) interaction of genotype and clenbuterol treatment, indicating that Mstn null mice were less responsive to clenbuterol compared with wild-type mice. Thus, for all other traits, the impact of Mstn null mutation and clenbuterol treatment was completely additive. These data suggest that disruption of Mstn function does not alter the response of mice to b-adrenergic agonists.

The objective of this experiment was to examine the resistance to diet‐induced obesity of myostatin (Mstn) null mice and determine if genes involved in thermogenesis were altered in these mice. Four‐week‐old male Mstn null and wild type mice were given ad libitum access to diets with 10 or 60% kcal from fat for 12 weeks. Glucose tolerance was determined after 0, 4, 8 and 12 weeks on diet. Body composition, muscle and fat pad weights, as well as other markers of metabolic syndrome were recorded and mRNA expression of several genes was examined in muscle, fat and liver. High‐fat fed mice consumed more calories and deposited weight and calories more efficiently than control mice. After 12 weeks of high‐fat feeding, body weight, body fat, fat pad weight, fasting blood glucose, serum insulin and leptin expression in adipose tissue were increased in both wild type and Mstn null mice. However, for all these parameters, the increase in Mstn null mice was less pronounced than in wild type mice indicating partial resistance to fat gain with excessive caloric consumption. Contrary to previous research, glucose tolerance was not altered in Mstn null mice. Furthermore, expression of some thermogenic genes including UCP‐3 and PGC1β were increased in adipose tissue of Mstn null mice fed high‐fat diets which may account for differences in obesity susceptibility.