## 4 Discussion and Interpretation
### Body and Tissue Weights (Table 3)  
The importance of SPARC is tissue development, embryogenesis, regeneration, its interaction with collagen and ECM, in addition to its role in collagen accumulation [59] would explain why _Sparc_ KO reduces body weight and SM weights, including the tibialis anterior muscle (correlated with what [PERSON] et al. reported [59]) in addition to other tissues (aorta and WAT), as a result of regeneration and development deficiency, similar to the decrease in bone mass (osteopenia) as a result of SPARC deficiency [56]. However, the observed increased weights or weight percentages of other tissues, such as the brain, liver and heart in _Sparc_ KO mice, could result from feedback signals. Indeed, the reduced development and metabolic deficiency in _Sparc_ KO mice would lead to the production of signals aiming to correct this developmental and metabolic deficiency (resulting from muscle low oxidation capacity, myokines secretion reduction, etc). Such signal effects would target selected tissues (those increased with _Sparc_ KO, such as the brain, which is the center of numerous neuroendocrine signals and in which [PERSON] et al., have shown that the neuronal activity levels of _Sparc_ KO mice are increased in the brain region dentate gyrus [82] which could support the hypothesis of such signals in _Sparc_ KO mice) and either be nonspecific or with insufficient impacts on other tissues (those for which _Sparc_ KO does not reduce the weights). For instance, the increased heart weight percentage in _Sparc_ KO mice could be adaptive to the fact that these mice have reduced oxidative phosphorylation ability (as shown by the low MT-CO1 expression) and would have more muscle-produced lactate. The developed heart could be an adaptation to the increased lactate production in order to increase the circulation and, therefore, increase lactate clearance, which could be taken by the liver to form glucose [80], which could also explain the increased weight (percentage) of the liver in _Sparc_ KO mice. Therefore, although _Sparc_ KO mice SM produced more lactate (weak oxidation capacity), they have the same blood lactate levels as WT mice because they would compensate via increased lactate blood clearance through enhanced blood circulation (increased heart weight percentage) combined to an increased intake by the liver (increased weight percentage), the brain (increased weight and weight percentage) and probably other tissues leading to that weight/weight percentage increase in those tissues in _Sparc_ KO mice. This correlates with the liver weight percentage for which we have Ex-KO\(>\)Ex-WT, meaning that, in the exercised groups, the liver (weight percentage) of _Sparc_ KO mice is superior to the liver (weight percentage) of WT mice (even though both had similar amount of training). This could indicate more tissue glycogen storage [83] (in a hydrated form that adds more water weight to the liver [84]) built from glucose made of the taken lactate because the _Sparc_ KO mice SM would produce more lactate (weak oxidative phosphorylation reflected by the decrease in MT-CO1 expression in the _Sparc_ KO mice) but clear it better through an increased blood circulation (increased heart weight percentage in _Sparc_ KO) combined with lactate uptake (clearance) by the liver [80] and also by the brain [80] (that also increased in weight in _Sparc_ KO mice) to compensate the low oxidation ability of the SM (supposed to contribute to lactate clearance but remains insufficient in terms of lactate clearance in _Sparc_ KO mice). Overall, there is no genotype-related difference in lactate level because there would be compensation. Indeed, whereas WT mice have good muscle lactate clearance (with low lactate production), _Sparc_ KO mice (although they have higher lactate production) have increased lactate clearance via the liver, brain, heart (that have increased weight percentage, compared to those in WT mice), etc.