Increased intramyocellular lipids but unaltered in vivo mitochondrial oxidative phosphorylation in skeletal muscle of adipose triglyceride lipase-deficient mice.

Adipose triglyceride lipase (ATGL) is a lipolytic enzyme that is highly specific for triglyceride hydrolysis. The ATGL-knockout mouse (ATGL(-/-)) accumulates lipid droplets in various tissues, including skeletal muscle, and has poor maximal running velocity and endurance capacity. In this study, we tested whether abnormal lipid accumulation in skeletal muscle impairs mitochondrial oxidative phosphorylation, and hence, explains the poor muscle performance of ATGL(-/-) mice. In vivo ¹H magnetic resonance spectroscopy of the tibialis anterior of ATGL(-/-) mice revealed that its intramyocellular lipid pool is approximately sixfold higher than in WT controls (P = 0.0007). In skeletal muscle of ATGL(-/-) mice, glycogen content was decreased by 30% (P < 0.05). In vivo ³¹P magnetic resonance spectra of resting muscles showed that WT and ATGL(-/-) mice have a similar energy status: [PCr], [P(i)], PCr/ATP ratio, PCr/P(i) ratio, and intracellular pH. Electrostimulated muscles from WT and ATGL(-/-) mice showed the same PCr depletion and pH reduction. Moreover, the monoexponential fitting of the PCr recovery curve yielded similar PCr recovery times (τPCr; 54.1 ± 6.1 s for the ATGL(-/-) and 58.1 ± 5.8 s for the WT), which means that overall muscular mitochondrial oxidative capacity was comparable between the genotypes. Despite similar in vivo mitochondrial oxidative capacities, the electrostimulated muscles from ATGL(-/-) mice displayed significantly lower force production and increased muscle relaxation time than the WT. These findings suggest that mechanisms other than mitochondrial dysfunction cause the impaired muscle performance of ATGL(-/-) mice.

The influence of food restriction versus ad libitum feeding of chow and purified diets on variation in body weight, growth and physiology of female Wistar rats.

Ad libitum (AL) supply of standard chow is the feeding method most often used for rodents in animal experiments. However, AL feeding is known to result in a shorter lifespan and decreased health as compared with restricted feeding. Restricted feeding and thus limiting calorie intake prevents many health problems, increases lifespan and can also increase group uniformity. All this leads to a reduced number of animals needed. So-called standard chows are known to be prone to variation in composition. Synthetic foods have a more standard composition, contributing to group uniformity which, like diet reduction, may decrease the number of animals necessary to obtain statistical significance. In this study, we compared the effects of AL versus restricted feeding (25% reduction in food intake) on standard chow versus synthetic food of three different suppliers on body weight (BW), growth, several blood parameters and organ weights in growing female Wistar rats over a period of 61 days. Diet restriction led to a decreased growth and significantly reduced variation in BW and growth as compared with AL feeding. AL feeding on synthetic diets caused a significantly higher BW gain than on chow diets. Due to experimental design, this same effect occurred on food restriction. Blood parameters and organ weights were affected neither by diet type nor by amount. Incidentally, variations were significantly reduced on food restriction versus AL, and on synthetic diets versus chow diets. This study demonstrates that food restriction versus AL feeding leads to a significantly reduced variation in BW and growth, thereby indicating the potential for reduction when applying this feeding schedule.