Publications by authors named "Serge Summermatter"
Article Synopsis
- - Multiple sclerosis (MS) is an autoimmune disease causing inflammation and damage in the central nervous system, leading to symptoms like muscle dysfunction that can affect mobility and quality of life.
- - Current treatments mainly focus on neuroinflammation, leaving a need for therapies targeting muscle function, as many people with MS experience skeletal muscle issues that can precede mobility-related disabilities.
- - Exercise, particularly aerobic and resistance training, is highlighted as an effective intervention to improve muscle strength, reduce fatigue, and enhance overall well-being in individuals with MS, emphasizing the importance of implementing these exercises early on.
Article Synopsis
- Musculoskeletal diseases are a major cause of mobility issues, often linked to muscle weakness, making resistance training a common treatment to boost strength.
- This study examines the chemerin pathway's role in inflammation and muscle function, finding that blocking a specific receptor (CMKLR1) can temporarily enhance strength but reduces endurance in mice.
- The research highlights the importance of CMKLR1 in muscle regeneration and contractility, suggesting potential for new drugs targeting this pathway to treat musculoskeletal and other diseases.
Article Synopsis
- Age-related loss of motor neurons affects muscle function, but the exact cause is still not well understood.
- Research on mice shows that neurotoxic microglia in the spinal cord play a role in this decline, as changes in motor units occur before muscle function decreases.
- Voluntary exercise and depleting harmful microglia can prevent or reverse this decline, suggesting that targeting these microglia might help maintain muscle health in aging.
Article Synopsis
- * Researchers created specific inhibitors targeting HDAC4 and uncovered three new proteins it modifies: myosin heavy chain, PGC-1α, and Hsc70, which play roles in muscle structure and metabolism.
- * Blocking HDAC4 can prevent muscle degradation and enhance metabolic pathways, hinting at potential new treatments for muscle disorders and other related diseases.
Mouse models of cancer-induced cachexia: Hind limb muscle mass and evoked force as readouts.
Biochem Biophys Res Commun
September 2018
Article Synopsis
- Advanced cancer patients commonly experience cachexia, a condition that leads to significant muscle loss and affects their treatment response, quality of life, and survival chances.
- There are currently no effective treatments for cachexia, highlighting the urgent need for early detection and monitoring of muscle mass loss to implement timely interventions.
- The study introduces simpler experimental cancer models using mice and human cancer cells, allowing for easier observation of muscle deterioration and evaluation of potential therapies for cachexia.
Article Synopsis
- This study investigates the expression of neuronal NO synthase (nNOS) isoforms in skeletal muscle and their relationship with mitochondrial content and activity, particularly focusing on the role of the PGC-1alpha coactivator.
- Research using various mouse models found that nNOS alpha-isoform predominates in type-2 oxidative muscle fibers and is linked to higher mitochondrial density, especially in the tibialis anterior muscle compared to other muscles.
- The findings suggest that nNOS alpha-isoform expression is positively regulated by PGC-1alpha, indicating a significant interaction between nNOS and mitochondrial signaling in oxidative muscle fibers.
Article Synopsis
- Metallothioneins are proteins that manage zinc storage and transport but are linked to increased levels during muscle atrophy.
- Blocking metallothioneins 1 and 2 activates the Akt pathway, leading to larger muscle fibers and improved muscle strength.
- The positive impact of metallothionein blockade on muscle mass and function also holds true even with glucocorticoid-induced atrophy, suggesting a potential treatment strategy for muscle wasting conditions.
Article Synopsis
- Cachexia is a common condition in advanced cancer patients that negatively impacts treatment effectiveness, quality of life, and survival, with the role of ActRII inhibition in this context still unclear.
- The study used a mouse model to test the effects of a neutralizing antibody (CDD866) against ActRII, in combination with two anti-cancer drugs, cisplatin and everolimus.
- Results showed that cisplatin worsened weight loss and skeletal muscle degradation, while CDD866 helped protect against muscle loss; everolimus also protected muscle, and combining it with CDD866 suggested potential additional benefits.
Article Synopsis
- Skeletal muscle mass loss and its dysfunction are associated with various diseases, but resistance exercise can enhance muscle size and function by activating the mTORC1 pathway.
- The study investigates the role of PGC-1α in muscle adaptations after a chronic overload and finds that while overload promotes muscle hypertrophy and a shift to a slower muscle type, it occurs independently of PGC-1α.
- Surprisingly, deleting PGC-1α did not impair force generation in overloaded muscles, indicating that PGC-1α may not be necessary for muscle remodeling in response to overload.
Article Synopsis
- PGC-1α is a key regulator of metabolic changes in skeletal muscle, particularly in response to exercise.
- It promotes the expression of LDH B while reducing LDH A and its regulator, which helps maintain balanced lactate levels in the blood.
- This coordination of the LDH complex by PGC-1α enhances muscle adaptations from training, leading to improved exercise performance and better metabolic health.
Article Synopsis
- The study focuses on the role of mTORC1 in regulating skeletal muscle mass, highlighting that its inactivation leads to muscle atrophy and less oxidative capacity, while activation has potential benefits for muscle growth and function.
- Experiments involved genetically altering mice to either delete the mTORC1 component raptor or the inhibitor TSC1, and analyzing the effects on muscle size and response to mechanical load and nerve input.
- Results showed that deleting raptor caused muscle atrophy, while knocking down TSC1 increased muscle fiber size and resistance to atrophy, although sustained TSC1 deletion resulted in atrophy in most muscles but boosted oxidative capacity.
Article Synopsis
- * Targeting exercise mediators like PGC-1α may improve physical activity and its effects, despite potential downsides in sedentary conditions.
- * Combining increased PGC-1α levels with exercise can improve glucose regulation and insulin sensitivity, offering a promising strategy for treating metabolic disorders.
Article Synopsis
- Skeletal muscle is highly adaptable and can change its characteristics in response to various stimuli through epigenetic mechanisms, but the role of nuclear receptor corepressor 1 (NCoR1) in muscle is not well understood.
- In studies with muscle-specific knockout mice, NCoR1 deletion resulted in increased peak oxygen consumption, reduced maximum force, and improved fatigue resistance, indicating its significant influence on muscle function.
- The research found that NCoR1 interacts with key metabolic regulators like PGC-1α, revealing opposing effects on muscle gene expression and highlighting the potential for targeting this transcriptional network in treating metabolic diseases.
Article Synopsis
- Catch-up growth, linked to increased risk of type 2 diabetes, is marked by high insulin levels and rapid fat recovery following periods of food restriction.
- In a rat study, refeeding on a high-fat diet was found to reduce the ability of adipose tissue to utilize glucose for fat production (de novo lipogenesis), leading to potential issues with glucose regulation.
- The research supports the idea that dietary fats can disrupt normal glucose handling by promoting insulin resistance in muscles and reducing fat storage capabilities in fat tissue, contributing to glucose intolerance during catch-up growth.
Article Synopsis
- Regular endurance exercise remodels skeletal muscle through a protein called PGC-1α, which aids in muscle fiber type switching and increases resistance to fatigue.
- Researchers found that overexpressing PGC-1α in mice leads to reduced calcium release from muscle cells and delayed calcium clearance after contraction, affecting muscle force production.
- PGC-1α plays a dual role in calcium signaling and skeletal muscle adaptation, ultimately resulting in reduced maximum force but enhanced fatigue resistance during prolonged activity.
Article Synopsis
- - PGC-1α enhances oxidative metabolism in skeletal muscle, specifically in the extensor digitorum longus (EDL) muscle, which typically has low levels of this protein and minimal oxidation activity.
- - Over-expressing PGC-1α leads to a balanced lipid oxidation process by balancing activators and inhibitors, ultimately promoting better metabolic control without harmful side products that could disrupt glucose homeostasis.
- - This study finds that increased PGC-1α levels preserve PI3K activity, a marker for insulin resistance, indicating that PGC-1α may promote metabolic flexibility and mimic the positive effects of endurance training without affecting insulin sensitivity in mice on a standard diet.
Article Synopsis
- Exercise boosts a response in skeletal muscle mainly through a protein called PGC-1α, which helps in burning fat for energy during long workouts.
- The study explored how higher levels of PGC-1α might aid in fat creation in muscle and discovered it activates a specific gene for fat production, boosting fat synthesis.
- Findings reveal that PGC-1α not only enhances fat formation but also links increased sugar absorption and metabolic pathways to support this process, showing its role in muscle recovery post-exercise.
Article Synopsis
- Physical activity is crucial for a healthy lifestyle, but the molecular processes behind its benefits are not fully understood due to a lack of suitable experimental models.
- Researchers developed an electrical stimulation method for muscle cells that mimics the gene expression changes seen in endurance-trained muscles, using PGC-1alpha as a key marker.
- The study revealed that the changes in gene expression in stimulated muscle cells closely resemble those in trained muscles rather than those seen after acute exercise, offering a valuable model to explore the molecular mechanisms of exercise adaptation.
Article Synopsis
- The study focuses on "catch-up growth," a process linked to an increased risk of type 2 diabetes, particularly examining how glucose is used by fat cells during this phase.
- Researchers used a rat model that simulates semistarvation followed by refeeding to study changes in fat tissue and glucose metabolism without increased food intake.
- Results indicated that during catch-up fat, fat cells increase in number and change in composition, while hyperinsulinemia and enhanced fat-making processes (lipogenesis) occur early, suggesting these changes are crucial for storing glucose in fat rather than muscle.
Article Synopsis
- The study explores how weight loss and recovery can lead to increased fat storage, known as catch-up fat, due to decreased thermogenesis influenced by signals from fat tissue.
- Researchers found that in a rat model of semistarvation followed by refeeding, levels of the gene SCD1 in skeletal muscle rise, linking this gene's activity to the process of fat recovery.
- Elevated SCD1 levels help convert fatty acids, reducing their oxidation in mitochondria, which ultimately slows down the body’s energy expenditure and plays a role in regulating fat stores.
Article Synopsis
- Catch-up growth is a process where rapid weight gain occurs, often leading to risks for obesity, type 2 diabetes, and cardiovascular diseases, characterized by high insulin levels and increased fat recovery.
- A study using rat models found that during this catch-up growth, insulin was less effective in stimulating glucose use in muscles but more effective in fat tissues, indicating a shift in how the body processes glucose and fat.
- The findings suggest that reduced body heat production (thermogenesis) may play a role in promoting fat recovery by causing insulin resistance in muscles and heightened insulin response in fat tissues, linking catch-up growth to future metabolic issues.
Article Synopsis
- Researchers studied how leptin affects respiration rates in mouse skeletal muscle and its interaction with metabolism using specific enzymes like PI3K and AMPK.
- *The findings indicate that leptin boosts heat production in muscle by promoting a cycle between fat production and fat burning, which relies on both PI3K and AMPK signaling pathways.
- *This process helps prevent excessive fat buildup in skeletal muscle, offering a new understanding of how leptin contributes to metabolic health.