Speeding up Growth: Selection for Mass-Independent Maximal Metabolic Rate Alters Growth Rates.

Investigations into relationships between life-history traits, such as growth rate and energy metabolism, typically focus on basal metabolic rate (BMR). In contrast, investigators rarely examine maximal metabolic rate (MMR) as a relevant metric of energy metabolism, even though it indicates the maximal capacity to metabolize energy aerobically, and hence it might also be important in trade-offs. We studied the relationship between energy metabolism and growth in mice (Mus musculus domesticus Linnaeus) selected for high mass-independent metabolic rates. Selection for high mass-independent MMR increased maximal growth rate, increased body mass at 20 weeks of age, and generally altered growth patterns in both male and female mice. In contrast, there was little evidence that the correlated response in mass-adjusted BMR altered growth patterns. The relationship between mass-adjusted MMR and growth rate indicates that MMR is an important mediator of life histories. Studies investigating associations between energy metabolism and life histories should consider MMR because it is potentially as important in understanding life history as BMR.

Selection for increased mass-independent maximal metabolic rate suppresses innate but not adaptive immune function.

Both appropriate metabolic rates and sufficient immune function are essential for survival. Consequently, eco-immunologists have hypothesized that animals may experience trade-offs between metabolic rates and immune function. Previous work has focused on how basal metabolic rate (BMR) may trade-off with immune function, but maximal metabolic rate (MMR), the upper limit to aerobic activity, might also trade-off with immune function. We used mice artificially selected for high mass-independent MMR to test for trade-offs with immune function. We assessed (i) innate immune function by quantifying cytokine production in response to injection with lipopolysaccharide and (ii) adaptive immune function by measuring antibody production in response to injection with keyhole limpet haemocyanin. Selection for high mass-independent MMR suppressed innate immune function, but not adaptive immune function. However, analyses at the individual level also indicate a negative correlation between MMR and adaptive immune function. By contrast BMR did not affect immune function. Evolutionarily, natural selection may favour increasing MMR to enhance aerobic performance and endurance, but the benefits of high MMR may be offset by impaired immune function. This result could be important in understanding the selective factors acting on the evolution of metabolic rates.

Metabolic rates associated with membrane fatty acids in mice selected for increased maximal metabolic rate.

Aerobic metabolism of vertebrates is linked to membrane fatty acid (FA) composition. Although the membrane pacemaker hypothesis posits that desaturation of FAs accounts for variation in resting or basal metabolic rate (BMR), little is known about the FA profiles that underpin variation in maximal metabolic rate (MMR). We examined membrane FA composition of liver and skeletal muscle in mice after seven generations of selection for increased MMR. In both liver and skeletal muscle, unsaturation index did not differ between control and high-MMR mice. We also examined membrane FA composition at the individual-level of variation. In liver, 18:0, 20:3 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In gastrocnemius muscle, 18:2 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In addition, muscle 16:1 n-7, 18:1 n-9, and 22:5 n-3 FAs were significant predictors of BMR, whereas no liver FAs were significant predictors of BMR. Our findings indicate that (i) individual variation in MMR and BMR appears to be linked to membrane FA composition in the skeletal muscle and liver, and (ii) FAs that differ between selected and control lines are involved in pathways that can affect MMR or BMR.

Effects of Selection for Mass-Independent Maximal Metabolic Rate on Food Consumption.

Metabolic rates potentially regulate the pace of important physiological and life-history traits. Natural selection has shaped the evolution of metabolic rates and the physiology that supports them, including digestibility and the rate of food consumption. Understanding the relationship between metabolic rates and energy internalization is central to understanding how resources are allocated among competing physiological functions. We investigated how artificial selection on mass-independent basal metabolic rate (BMR) and mass-independent aerobic maximal metabolic rate (MMR) affected food consumption and apparent digestibility in mice. Evolved changes in mass-corrected BMR-but not mass-corrected MMR-corresponded with changes in food consumption. This result is consistent with previous work showing that BMR constitutes a large portion of an animal's daily energy budget and thus that BMR might provide a better indicator of daily food requirements than MMR. In contrast, digestive efficiencies did not differ among selection treatments and did not evolve in these mice. This study provides insights into how evolution of metabolic rates may affect food consumption and overall energy use.

Genetic variances and covariances of aerobic metabolic rates in laboratory mice.

The genetic variances and covariances of traits must be known to predict how they may respond to selection and how covariances among them might affect their evolutionary trajectories. We used the animal model to estimate the genetic variances and covariances of basal metabolic rate (BMR) and maximal metabolic rate (MMR) in a genetically heterogeneous stock of laboratory mice. Narrow-sense heritability (h(2)) was approximately 0.38 +/- 0.08 for body mass, 0.26 +/- 0.08 for whole-animal BMR, 0.24 +/- 0.07 for whole-animal MMR, 0.19 +/- 0.07 for mass-independent BMR, and 0.16 +/- 0.06 for mass-independent MMR. All h(2) estimates were significantly different from zero. The phenotypic correlation of whole animal BMR and MMR was 0.56 +/- 0.02, and the corresponding genetic correlation was 0.79 +/- 0.12. The phenotypic correlation of mass-independent BMR and MMR was 0.13 +/- 0.03, and the corresponding genetic correlation was 0.72 +/- 0.03. The genetic correlations of metabolic rates were significantly different from zero, but not significantly different from one. A key assumption of the aerobic capacity model for the evolution of endothermy is that BMR and MMR are linked. The estimated genetic correlation between BMR and MMR is consistent with that assumption, but the genetic correlation is not so high as to preclude independent evolution of BMR and MMR.

Metabolic support of moderate activity differs from patterns seen after extreme behavior in the desert iguana Dipsosaurus dorsalis.

This study examined glucose and lactate metabolism in an iguanid lizard, Dipsosaurus dorsalis, during rest and after activity patterned on field behavior (15 s of running at 1 m/s). Metabolite oxidation and incorporation into glycogen by the whole animal, the liver, and oxidative and glycolytic muscle fibers were measured using (14)C- and (13)C-labeled compounds. Results showed that lactate metabolism is more responsive to changes that occurred between rest and recovery, whereas glucose appears to play a more steady state role. After activity, lactate oxidation produced 57 times as much ATP during 1 h of recovery than did glucose oxidation. However, lactate oxidation rates were elevated for only 30 min after activity, while glucose oxidation remained elevated beyond 1 h. Lactate was the primary source for glycogen synthesis during recovery, and glucose was the main glycogenic substrate during rest. This study supports previous research showing that brief activity in D. dorsalis is primarily supported by glycolysis and phosphocreatine breakdown, but it also suggests that there may be less of a reliance on glycolysis and a greater reliance on phosphocreatine than previously shown. The findings presented here indicate that the metabolic consequences of the behaviorally relevant activity studied are less severe than has been suggested by studies using more extreme activity patterns.

Muscle activation patterns and motor anatomy of Anna's hummingbirds Calypte anna and zebra finches Taeniopygia guttata.

Flying animals exhibit profound transformations in anatomy, physiology, and neural architecture. Although much is known about adaptations in the avian skeleton and musculature, less is known about neuroanatomy and motor unit integration for bird flight. Hummingbirds are among the most maneuverable and specialized of vertebrate fliers, and two unusual neuromuscular features have been previously reported: (1) the pectoralis major has a unique distribution pattern of motor end plates (MEPs) compared with all other birds and (2) electromyograms (EMGs) from the hummingbird's pectoral muscles, the pectoralis major and the supracoracoideus, show activation bursts composed of one or a few spikes that appear to have a very consistent pattern. Here, we place these findings in a broader context by comparing the MEPs, EMGs, and organization of the spinal motor neuron pools of flight muscles of Anna's hummingbird Calypte anna, zebra finches Taeniopygia guttata, and, for MEPs, several other species. The previously shown MEP pattern of the hummingbird pectoralis major is not shared with its closest taxonomic relative, the swift, and appears to be unique to hummingbirds. MEP arrangements in previously undocumented wing muscles show patterns that differ somewhat from other avian muscles. In the parallel-fibered strap muscles of the shoulder, MEP patterns appear to relate to muscle length, with the smallest muscles having fibers that span the entire muscle. MEP patterns in pennate distal wing muscles were the same regardless of size, with tightly clustered bands in the middle portion of the muscle, not evenly distributed bands over the muscle's entire length. Muscle activations were examined during slow forward flight in both species, during hovering in hummingbirds, and during slow ascents in zebra finches. The EMG bursts of a wing muscle, the pronator superficialis, were highly variable in peak number, size, and distribution across wingbeats for both species. In the pectoralis major, although the individual EMG bursts were much shorter in duration in hummingbirds relative to zebra finches, the variables describing the normalized amplitude and area of the activation bursts were otherwise indistinguishable between taxa during these flight modes. However, the degree of variation in the time intervals between EMG peaks was much lower in hummingbirds, which is a plausible explanation for the "patterned" EMG signals reported previously.

Metabolomics of aerobic metabolism in mice selected for increased maximal metabolic rate.

Maximal aerobic metabolic rate (MMR) is an important physiological and ecological variable that sets an upper limit to sustained, vigorous activity. How the oxygen cascade from the external environment to the mitochondria may affect MMR has been the subject of much interest, but little is known about the metabolic profiles that underpin variation in MMR. We tested how seven generations of artificial selection for high mass-independent MMR affected metabolite profiles of two skeletal muscles (gastrocnemius and plantaris) and the liver. MMR was 12.3% higher in mass selected for high MMR than in controls. Basal metabolic rate was 3.5% higher in selected mice than in controls. Artificial selection did not lead to detectable changes in the metabolic profiles from plantaris muscle, but in the liver amino acids and tricarboxylic acid cycle (TCA cycle) metabolites were lower in high-MMR mice than in controls. In gastrocnemius, amino acids and TCA cycle metabolites were higher in high-MMR mice than in controls, indicating elevated amino acid and energy metabolism. Moreover, in gastrocnemius free fatty acids and triacylglycerol fatty acids were lower in high-MMR mice than in controls. Because selection for high MMR was associated with changes in the resting metabolic profile of both liver and gastrocnemius, the result suggests a possible mechanistic link between resting metabolism and MMR. In addition, it is well established that diet and exercise affect the composition of fatty acids in muscle. The differences that we found between control lines and lines selected for high MMR demonstrate that the composition of fatty acids in muscle is also affected by genetic factors.