Phenotypic diversity between laboratory mouse strains provides a model for studying the underlying genetic mechanisms. The A/J strain performs poorly in various endurance exercise models. The aim of the study was to test if endurance capacity and contractility of the fast- and slow-twitch muscles are affected by the genes on mouse chromosome 10. The C57BL/6J (B6) strain and C57BL/6J-Chr 10A/J/NaJ (B6.A10) consomic strain which carries the A/J chromosome 10 on a B6 strain background were compared. The B6.A10 mice compared to B6 were larger in body weight (p<0.02): 27.2 ± 1.9 vs. 23.8 ± 2.7 and 23.4 ± 1.9 vs. 22.9 ± 2.3 g, for males and females, respectively, and in male soleus weight (p<0.02): 9.7 ± 0.4 vs 8.6 ± 0.9 mg. In the forced running test the B6.A10 mice completed only 64% of the B6 covered distance (p<0.0001). However, there was no difference in voluntary wheel running (p=0.6) or in fatigability of isolated soleus (p=0.24) or extensor digitorum longus (EDL, p=0.7) muscles. We conclude that chromosome 10 of the A/J strain contributes to reduced endurance performance. We also discuss physiological mechanisms and methodological aspects relevant to interpretation of these findings.

Myostatin dysfunction promotes muscle hypertrophy, which can complicate assessment of muscle properties. We examined force generating capacity and creatine kinase (CK) efflux from skeletal muscles of young mice before they reach adult body and muscle size. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of Berlin high (BEH) mice with dysfunctional myostatin, i.e., homozygous for inactivating myostatin mutation, and with a wild-type myostatin (BEH+/+) were studied. The muscles of BEH mice showed faster (P < 0.01) twitch and tetanus contraction times compared with BEH+/+ mice, but only EDL displayed lower (P < 0.05) specific force. SOL and EDL of age-matched but not younger BEH mice showed greater exercise-induced CK efflux compared with BEH+/+ mice. In summary, myostatin dysfunction leads to impairment in muscle force generating capacity in EDL and increases susceptibility of SOL and EDL to protein loss after exercise.

Obesity is increasingly recognized not only as a metabolic disorder but also as a condition marked by the structural and functional deterioration of skeletal muscle and tendon tissues. Central to this process is the dysregulation of the extracellular matrix (ECM) resulting in fibrosis and ectopic fat accumulation, factors that contribute to impaired tissue mechanics. Myostatin (GDF-8), a member of the TGF-β superfamily, is known as a negative regulator of muscle mass. It can also mediate interaction between adipose and other tissues including muscles and tendons. In obesity, elevated myostatin levels have been reported to be associated with insulin resistance, muscle atrophy, and activation of SMAD2/3 signaling, while experimental and preclinical studies indicate that myostatin inhibition can improve glucose homeostasis and increase lean mass. Emerging evidence suggests that myostatin also plays a critical role in muscle ECM and tendon remodeling. Restoring its physiological levels may help reverse ECM disorganization and reduce tissue fragility associated with musculotendinous dysfunction. This review highlights the multifaceted role of myostatin in obesity, beyond its role in muscle catabolism, to include modulation of structural integrity, metabolism, and mechanical adaptability of the musculotendinous system. Understanding how myostatin responds to metabolic stress and affects biomechanical remodeling offers novel insights into obesity-related muscle and tendon dysfunction.

Caloric restriction (CR) is of key importance in combating obesity and its associated diseases. We aimed to examine effects of dietary macronutrient distribution on weight loss and metabolic health in obese mice exposed to CR. Male C57BL/6J mice underwent diet-induced obesity for 18 weeks. Thereafter mice were exposed to a 6-week CR for up to 40% on either low-fat diet (LFD; 20, 60, 20% kcal from protein, carbohydrate, fat), low-carb diet (LCD; 20, 20, 60% kcal, respectively) or high-pro diet (HPD; 35, 35, 30% kcal, respectively) (n = 16 each). Ten mice on the obesogenic diet served as age-matched controls. Body composition was evaluated by tissue dissections. Glucose tolerance, bloods lipids and energy metabolism were measured. CR-induced weight loss was similar for LFD and LCD while HPD was associated with a greater weight loss than LCD. The diet groups did not differ from obese controls in hindlimb muscle mass, but showed a substantial decrease in body fat without differences between them. Glucose tolerance and blood total cholesterol were weight-loss dependent and mostly improved in LFD and HPD groups during CR. Blood triacylglycerol was lowered only in LCD group compared to obese controls. Thus, CR rather than macronutrient distribution in the diet plays the major role for improvements in body composition and glucose control in obese mice. Low-carbohydrate-high-fat diet more successfully reduces triacylglycerol but not cholesterol levels compared to isocaloric high-carbohydrate-low-fat weight loss diets.