Analysis Tools
cellular
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• wild-type and mutant skeletal muscle displayed no differences in fatty acid or glucose oxidation at rest and post-exercise
• in mutant skeletal muscle, mitochondria were more coupled (i.e. increased state 3/state 4 ratio); however, no alterations in whole animal oxygen consumption were observed
• in mutant skeletal muscle, mutant mitochondria produced more reactive oxygen species (ROS) relative to wild-type
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• the mean ATP:ADP ratio in skeletal muscle of each individual mouse is significantly higher in 5-7 month old mutant mice than in age- and weight-matched controls, although the means for mutant and control groups do not differ significantly
• the in vivo rate constant for ATP synthesis from Pi, determined using a combination of isotope labeling and NMR, in skeletal muscle is 2-fold greater in fasting 5-7 month old mutant mice than in age- and weight-matched controls
• the rate of ATP synthesis in skeletal muscle of fasting 5-7 month old mutant mice, calculated from the rate constant and Pi concentration, is approximately 4-fold that in age- and weight-matched control mice
• the in vivo index of mitochondrial coupling, calculated as the ratio of fasting ATP synthesis to tricarboxylic acid cycle (TCA) cycle flux rates, is 2-4-fold greater in skeletal muscle of mutant than of age- and weight-matched control mice; this presumably is due to the higher rate of ATP synthesis in mutant mice, as it was determined from the time course of glutamate C3 and C4 enrichment following infusion of [2-13C]acetate that the TCA flux rates are similar in skeletal muscle of fasting mutant and control mice
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growth/size/body
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• homozygotes were grossly normal and did not develop obesity
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homeostasis/metabolism
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• homozygotes showed no differences in body weight, triglyceride content or food intake relative to wild-type
• homozygotes displayed normal physical performance during acute exercise relative to wild-type
• only male homozygotes challenged with a high-fat diet tended to be heavier; however, this was not statistically significant
• homozygotes displayed a normal thermogenic adaptation to cold
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• newborn (P4-P6 days) and young mutant mice (6 weeks) showed no differences in blood fatty acid levels relative to wild-type
• older mutants (18-24-weeks) tended to have higher fatty acid levels in blood that reached statistical significance when challenged with a high-fat diet
• the in vivo index of mitochondrial coupling, calculated as the ratio of fasting ATP synthesis to TCA cycle flux rates, is 2-4-fold greater in skeletal muscle of mutant than of age- and weight-matched control mice; this presumably is due to the higher rate of ATP synthesis in mutant mice, as it was determined from the time course of glutamate C3 and C4 enrichment following infusion of [2-13]acetate that the tricarboxylic acid cycle (TCA) flux rates are similar in skeletal muscle of fasting mutant and control mice
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