Effect of exercise on mouse liver and brain bioenergetic infrastructures

New Findings What is the central question of this study? Although exercise is shown to benefit different organs, little research has focused on the mitochondrial response to exercise training in the liver and brain. Also, why and how exercise‐induced muscle activation modifies non‐muscle tissues is not fully understood. What is the main finding and its importance? We found a dissociated mitochondrial biogenesis, in which some components for gluconeogenesis are enhanced while others for oxidative phosphorylation are minimized, in the livers of exercised mice. These observations suggest that mitochondrial biogenesis is not necessarily an all‐or‐none process, but rather can be strategically tailored to meet a specific tissue's particular physiological needs. Also, this is the first manuscript to show the possible role of exercise‐induced lactate production in mediating exercise's effects on non‐muscle tissues. To assess the effects of exercise on liver and brain bioenergetic infrastructures, we exposed C57BL/6 mice to 6 weeks of moderate‐intensity treadmill exercise. During the training period, fasting blood glucose was lower in exercised mice than in sedentary mice, but serum insulin levels were not reduced. At week 6, trained mice showed a paradoxical decrease in plasma lactate during exercise, which was accompanied by an increase in the liver monocarboxylate transporter 2 protein level (∼30%, P < 0.05). Exercise increased liver peroxisomal proliferator‐activated receptor‐γ coactivator 1α expression (approximately twofold, P < 0.001), NAD‐dependent deacetylase sirtuin‐1 protein (∼30%, P < 0.05), p38 protein (∼15%, P < 0.05), cytochrome c oxidase subunit 4 isoform 1 protein (∼50%, P < 0.05) and AMP‐activated protein kinase phosphorylation (∼40%, P < 0.05). Despite this, liver mitochondrial DNA copy number (∼30%, P = 0.05), mitochondrial transcription factor A expression (∼15%, P < 0.05), cytochrome c oxidase subunit 2 expression (∼10%, P < 0.05), cAMP‐response element binding protein phosphorylation (∼60%, P < 0.05) and brain‐derived neurotrophic factor expression (∼40%, P < 0.05) were all reduced, while cytochrome oxidase and citrate synthase activities were unchanged. The only altered brain parameter observed was a reduction in tumour necrosis factor α expression (∼35%, P < 0.05); tumour necrosis factor α expression was unchanged in liver. Our data suggest that lactate produced by exercising muscle modifies the liver bioenergetic infrastructure, and enhanced liver uptake may in turn limit the ability of exercise‐generated lactate to modify brain bioenergetics. Also, it appears that, at least in the liver, a dissociated mitochondrial biogenesis, in which some components are strategically enhanced while others are minimized, can occur.