PGC-1 α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice

Applied Physiology, Nutrition, and Metabolism, Ahead of Print. Cancer cachexia (CC) accounts for 20% –40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxisome proliferator-activated recepto r γ coactivator-1 α (PGC-1α). First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant MitoTEMPO (MitoT) attenuates myotube atrophy induced by Lewis lung carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle-specific PGC-1α overexpressing (MCK-PCG1α) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1α did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and ∼11-fold greater in WT-LLC vs WT-phosphate-buffered saline (PBS) for males and females, respectively (p <  0.05). MitoTimer red:green ratio for male PGC was ∼65% higher than WT groups (p <  0.05), with ∼3-fold more red puncta in LLC than PBS (p <  0.05). Red:green ratio was ∼56% lower in females WT-LLC vs PGC-LLC (p <  0.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was ∼73% and 2-fold higher in male and female LLC mice, respectively, vs PBS (p <  0.05). While MitoT could mitigate cancer-induced atrophy in vitro, PGC-1α ov...
Source: Applied Physiology, Nutrition, and Metabolism - Category: Physiology Authors: Source Type: research