Physiological and biochemical adaptations to training in Rana pipiens

Fifteen Rana pipiens were trained on a treadmill thrice weekly for 6.5 weeks to assess the effects of training on an animal that supports activity primarily through anaerobiosis. Endurance for activity increased 35% in these frogs as a result of training ( P =0.006, Fig. 1). This increased performance was not due to enhanced anaerobiosis. Total lactate produced during exercise did not differ significantly for the trained or untrained animals in either gastrocnemius muscle (2.77±0.21 and 2.82±0.13 mg/g, respectively) or whole body (1.32±0.10 and 1.47±0.06 mg/g, respectively). Glycogen depletion also did not differ between the two groups (Fig. 2c). The primary response to training appeared to involve augmentation of aerobic metabolism, a response similar to that reported for mammals. Gastrocnemius muscles of trained frogs underwent a 38% increase over those of untrained individuals in the maximum activity of citrate synthase (14.5±1.0 and 10.5±0.9 μmoles/(g wet wt·min); P =0.008). This enzyme was also positively correlated with the level of maximum performance for all animals tested ( r =0.61, P <0.01) and with the degree of improvement in the trained animals ( r =0.72, P <0.05). In addition to an increased aerobic capacity, the trained animals demonstrated a greater removal of lactate from the muscle 15 min after fatigue (Fig. 2b).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47124/1/360_2004_Article_BF00710002.pd

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Lipid metabolism, exercise and insulin action

Skeletal muscle constitutes 40% of body mass and takes up 80% of a glucose load. Therefore, impaired glucose removal from the circulation, such as that which occurs in obesity and type 2 diabetes, is attributable in large part to the insulin resistance in muscle. Recent research has shown that fatty acids, derived from adipose tissue, can interfere with insulin signalling in muscle. Hence, insulin-stimulated GLUT4 translocation to the cell surface is impaired, and therefore, the rate of glucose removal from the circulation into muscle is delayed. The mechanisms provoking lipid-mediated insulin resistance are not completely understood. In sedentary individuals, excess intramyocellular accumulation of triacylglycerols is only modestly associated with insulin resistance. In contrast, endurance athletes, despite accumulating large amounts of intramyocellular triacylglycerols, are highly insulin sensitive. Thus it appears that lipid metabolites, other than triacylglycerols, interfere with insulin signalling. These metabolites, however, are not expected to accumulate in athletic muscles, as endurance training increases the capacity for fatty acid oxidation by muscle. These observations, and others in severely obese individuals and type 2 diabetes patients, suggest that impaired rates of fatty acid oxidation are associated with insulin resistance. In addition, in obesity and type 2 diabetes, the rates of fatty acid transport into muscle are also increased. Thus, excess intracellular lipid metabolite accumulation, which interferes with insulin signalling, can occur as a result of impaired rates of fatty acid oxidation and/or increased rates of fatty acid transport into muscle. Accumulation of excess intramyocellular lipid can be avoided by exercise, which improves the capacity for fatty acid oxidation

Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment

10.1152/ajpregu.00190.2009American Journal of Physiology - Regulatory Integrative and Comparative Physiology2986R1692-R1699AJPR