Leucine Supplementation Exacerbates Morbidity in Male but Not Female Mice with Colorectal Cancer-Induced Cachexia.

Cancer cachexia (CC) is a multifactorial wasting syndrome characterized by a significant loss in lean and/or fat mass and represents a leading cause of mortality in cancer patients. Nutraceutical treatments have been proposed as a potential treatment strategy to mitigate cachexia-induced muscle wasting. However, contradictory findings warrant further investigation.

Development of skeletal muscle fibrosis in a rodent model of cancer cachexia.

Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes.

Effects of PGC-1α overexpression on the myogenic response during skeletal muscle regeneration.

The ability of skeletal muscle to regenerate from injury is crucial for locomotion, metabolic health, and quality of life. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1A) is a transcriptional coactivator required for mitochondrial biogenesis. Increased mitochondrial biogenesis is associated with improved muscle cell differentiation, however PGC1A's role in skeletal muscle regeneration following damage requires further investigation.

Mitochondrial aberrations during the progression of disuse atrophy differentially affect male and female mice.

Background: Disuse decreases muscle size and is predictive of mortality across multiple pathologies. Detriments to mitochondrial function are hypothesized to underlie disuse-induced muscle atrophy. Little data exist on early mechanisms contributing to onset of these pathologies, nor is it known how they differ between sexes.

Cancer-induced Cardiac Atrophy Adversely Affects Myocardial Redox State and Mitochondrial Oxidative Characteristics.

Unlabelled: Cachexia presents in 80% of advanced cancer patients; however, cardiac atrophy in cachectic patients receives little attention. This cardiomyopathy contributes to increased occurrence of adverse cardiac events compared to age-matched population norms. Research on cardiac atrophy has focused on remodeling; however, alterations in metabolic properties may be a primary contributor.

The effect of autologous repair and voluntary wheel running on force recovery in a rat model of volumetric muscle loss.

New Findings: What is the central question of this study? Following large traumatic loss of muscle tissue (volumetric muscle loss; VML), permanent functional and cosmetic deficits present themselves and regenerative therapies alone have not been able to generate a robust regenerative response: how does the addition of rehabilitative therapies affects the regenerative response? What is the main finding and its importance? Using exercise along with autologous muscle repair, we demonstrated accelerated muscle force recovery response post-VML. The accentuated force recovery 2 weeks post-VML would allow patients to return home sooner than allowed with current therapies.

Abstract: Skeletal muscle can regenerate from damage but is overwhelmed with extreme tissue loss, known as volumetric muscle loss (VML).

Moderators of skeletal muscle maintenance are compromised in sarcopenic obese mice.

The purpose of this study was to determine whether sarcopenic obesity accelerates impairments in muscle maintenance through the investigation of cell cycle progression and myogenic, inflammatory, catabolic and protein synthetic signaling in mouse gastrocnemius muscles. At 4 weeks old, 24 male C57BL/6 mice were fed either a high fat diet (HFD, 60 % fat) or normal chow (NC, 17 % fat) for either 8-12 weeks or 21-23 months. At 3-4 months or 22-24 months the gastrocnemius muscles were excised.

Comparative plasma proteomics in muscle atrophy during cancer-cachexia and disuse: The search for atrokines.

Skeletal muscle atrophy is common across a variety of pathologies. Underlying mechanisms of atrophy differ between pathologies, and in many conditions, circulating factors are tied to muscle atrophy. Therefore, we sought to identify alterations to the plasma proteome across divergent forms of muscle atrophy, disuse and cancer cachexia, as potential mediators of atrophy.

Altering aspects of mitochondrial quality to improve musculoskeletal outcomes in disuse atrophy.

Muscle atrophy is a significant moderator for disease prognosis; as such, interventions to mitigate disuse-induced muscle loss are imperative to improve clinical interventions. Mitochondrial deteriorations may underlie disuse-induced myopathies; therefore, improving mitochondrial quality may be an enticing therapeutic intervention. However, different mitochondria-based treatments may have divergent impacts on the prognosis of disuse atrophy.

Neither autophagy nor exercise training mode affect exercise-induced beneficial adaptations in high fat-fed mice.

Unlabelled: Exercise mitigates obesity-associated pathologies; however, there is controversy regarding optimal exercise interventions. Autophagy, is known to decrease during obesity and is an important moderator for exercise adaptations.

Purpose: To investigate individual and combined effects of different exercise interventions and autophagy inhibition on exercise adaptations during obesity.

Hepatic alterations during the development and progression of cancer cachexia.

Cancer-associated bodyweight loss (cachexia) is a hallmark of many cancers and is associated with decreased quality of life and increased mortality. Hepatic function can dramatically influence whole-body energy expenditure and may therefore significantly influence whole-body health during cancer progression. The purpose of this study was to examine alterations in markers of hepatic metabolism and physiology during cachexia progression.

Mitochondrial mRNA translation initiation contributes to oxidative metabolism in the myocardia of aged, obese mice.

Unlabelled: Being both advanced in age and obese each contribute to cardiac hypertrophy in a unique manner. Electron transport complexes I and IV are implicated in deficient electron transport during cardiomyopathies and contain the majority of protein subunits that are transcribed and translated by machinery localized within the mitochondria.

Purpose: To assess myocardial mt-mRNA translation factors in relation to mitochondrial content and mtDNA-encoded protein using a mouse model of aged obesity and to test the relationship of mt-mRNA translation initiation factor 2 (mtIF2) to oxidative capacity and the cellular oxidation-reduction (redox) state in cardiomyocytes.

Protein imbalance in the development of skeletal muscle wasting in tumour-bearing mice.

Background: Cancer cachexia occurs in approximately 80% of cancer patients and is a key contributor to cancer-related death. The mechanisms controlling development of tumour-induced muscle wasting are not fully elucidated. Specifically, the progression and development of cancer cachexia are underexplored.

Transcriptomic analysis of the development of skeletal muscle atrophy in cancer-cachexia in tumor-bearing mice.

Cancer-cachexia (CC) is a wasting condition directly responsible for 20-40% of cancer-related deaths. The mechanisms controlling development of CC-induced muscle wasting are not fully elucidated. Most investigations focus on the postcachectic state and do not examine progression of the condition.

Cardiac hypertrophy in sarcopenic obese C57BL/6J mice is independent of Akt/mTOR cellular signaling.

Unlabelled: Sarcopenic obesity (SO) is the comorbidity of age-related muscle wasting and obesity. SO increases the risk of heart disease, but little is known about the cellular signaling in cardiac muscle of SO individuals.

Aim: The purpose of this study was to identify key cellular signaling alterations in cardiac muscle of sarcopenic obese mice.

Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice.

Background: Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20-40% of cancer-related deaths. Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degeneration precedes muscle wasting in cancer cachexia.

Autophagy activation, not peroxisome proliferator-activated receptor γ coactivator 1α, may mediate exercise-induced improvements in glucose handling during diet-induced obesity.

What is the central question of this study? What are the individual and combined effects of muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) overexpression and physical activity during high-fat feeding on glucose and exercise tolerance? What is the main finding and its importance? Our main finding is that muscle-specific PGC-1α overexpression provides no protection against lipid-overload pathologies nor does it enhance exercise adaptations. Instead, physical activity, regardless of PGC-1α content, protects against high-fat diet-induced detriments. Activation of muscle autophagy was correlated with exercise protection, suggesting that autophagy might be a mediating factor for exercise-induced protection from lipid overload.