scholarly journals Interspecies Differences in Activation of Peroxisome Proliferator-Activated Receptor γ by Pharmaceutical and Environmental Chemicals

2021 ◽  
Author(s):  
Clémentine Garoche ◽  
Abdelhay Boulahtouf ◽  
Marina Grimaldi ◽  
Barbara Chiavarina ◽  
Lucia Toporova ◽  
...  
Keyword(s):  
Environmental Chemicals ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interspecies Differences

Origins of interspecies variation in mammalian muscle metabolic enzymes

2011 ◽  
Vol 43 (14) ◽  
pp. 873-883 ◽  
Author(s):  
K. M. Kocha ◽  
C. E. Genge ◽  
C. D. Moyes
Keyword(s):  
Tibialis Anterior ◽  
Regulatory Element ◽  
Element Distribution ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Interspecies Differences ◽  
Interspecies Variation ◽  
Nuclear Respiratory Factor 1

Do the transcriptional mechanisms that control an individual's mitochondrial content, PGC1α (peroxisome proliferator-activated receptor γ coactivator-1α) and NRF1 (nuclear respiratory factor-1), also cause differences between species? We explored the determinants of cytochrome c oxidase (COX) activities in muscles from 12 rodents differing 1,000-fold in mass. Hindlimb muscles differed in scaling patterns from isometric (soleus, gastrocnemius) to allometric (tibialis anterior, scaling coefficient = −0.16). Consideration of myonuclear domain reduced the differences within species, but interspecies differences remained. For tibialis anterior, there was no significant scaling relationship in mRNA/g for COX4-1, PGC1α, or NRF1, yet COX4-1 mRNA/g was a good predictor of COX activity (r2 = 0.55), PGC1α and NRF1 mRNA correlated with each other (r2 = 0.42), and both could predict COX4-1 mRNA (r2 = 0.48 and 0.52) and COX activity (r2 = 0.55 and 0.49). This paradox was resolved by multivariate analysis, which explained 90% of interspecies variation, about equally partitioned between mass effects and PGC1α (or NRF1) mRNA levels, independent of mass. To explore the determinants of PGC1α mRNA, we analyzed 52 mammalian PGC1α proximal promoters and found no size dependence in regulatory element distribution. Likewise, the activity of PGC1α promoter reporter genes from 30 mammals showed no significant relationship with body mass. Collectively, these studies suggest that not all muscles scale equivalently, but for those that show allometric scaling, transcriptional regulation of the master regulators, PGC1α and NRF1, does not account for scaling patterns, though it does contribute to interspecies differences in COX activities independent of mass.

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