Abstract
Cancer associated body wasting is the cause of physical disability, reduced tolerance to anticancer therapy and reduced survival of cancer patients and, similarly to cancer, its incidence is increasing. There is no cure for this clinical condition, and the pathophysiological process involved is largely unknown. Exercise training appears as the gold standard non-pharmacological therapy for the management of this wasting syndrome. Herein we used a lipidomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS) to study the effect of exercise in the modulation of phospholipids profile of mitochondria isolated from gastrocnemius muscle of a pre-clinical model of urothelial carcinoma-related body wasting (BBN induced), submitted to 13 weeks of treadmill exercise after diagnosis. Multivariate analysis showed a close relationship between the BBN exercise group and both control groups (control sedentary and control exercise), while the BBN sedentary group was significantly separated from the control groups and the BBN exercise group. Univariate statistical analysis revealed differences mainly in phosphatidylserine (PS) and cardiolipin (CL), although some differences were also observed in phosphatidylinositol (PI, LPI) and phosphatidylcholine (PC) phospholipids. PS with shorter fatty acyl chains were up-regulated in the BBN sedentary group, while the other species of PS with longer FA and a higher degree of unsaturation were down-regulated, but the BBN exercise group was mostly similar to control groups. Remarkably, exercise training prevented these alterations and had a positive impact on the ability of mitochondria to produce ATP, restoring the healthy phospholipid profile. The remodelling of mitochondria phospholipid profile in rats with urothelial carcinoma allowed confirming the importance of the lipid metabolism in mitochondria dysfunction in cancer-induced skeletal muscle remodelling. The regulation of phospholipid biosynthetic pathways observed in the BBN exercise group supported the current perspective that exercise is an adequate therapeutic approach for the management of cancer-related muscle remodeling.
Highlights
The incidence of cancer has increased in the last years and, paraneoplastic syndromes such as cachexia have increased
We use a lipidomics MS-based approach to study the effect of exercise in the modulation of phospholipids profile of mitochondria isolated from gastrocnemius muscle of a pre-clinical model of urothelial carcinoma-related body wasting submitted to 13 weeks of treadmill exercise after diagnosis
The phospholipidome of the total lipid extracts obtained from mitochondria of control rats (CTsed), healthy rats undertaking exercise (CTex), rats with urothelial carcinoma (BBNsed), and rats with urothelial carcinoma and submitted to exercise training (BBNex), were analysed by HILIC-MS and MS/MS and statistic analysis
Summary
The incidence of cancer has increased in the last years and, paraneoplastic syndromes such as cachexia have increased. Cachexia is an insidious syndrome associated with cancer, estimated to occur in 60–80% of the cases, and is mainly characterized by body weight decrease due to skeletal muscle loss[1,2]. This muscle wasting contributes to physical disability, weakness, reduced tolerance to anticancer therapy and reduced survival of cancer patients[1,2]. The benefits of exercise training on skeletal muscle involves mitochondrial adaptations mainly characterized by increased mitochondrial biogenesis, which are linked to improved metabolic health[20]. The identification of changes in the phospholipid profile permits to hypothesize about the physiological processes involved, and possible biomarkers and therapeutic targets of cancer-related muscle remodelling and physical exercise beneficial role
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