scholarly journals SOD2 in Skeletal Muscle: New Insights from an Inducible Deletion Model

2021 ◽  
Author(s):  
Aowen Zhuang ◽  
Christine Yang ◽  
Yingying Liu ◽  
Yanie Tan ◽  
Simon T Bond ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Whole Body ◽  
Skeletal Muscle Function ◽  
Muscle Lipid ◽  
Transport Chain ◽  
Lipid Species ◽  
Intracellular Ros ◽  
Metabolic Conditions ◽  
Whole Body Metabolism ◽  
Old Mice

Metabolic conditions such as obesity, insulin resistance and glucose intolerance are frequently associated with impairments in skeletal muscle function and metabolism. This is often linked to dysregulation of homeostatic pathways including an increase in reactive oxygen species (ROS) and oxidative stress. One of the main sites of ROS production is the mitochondria, where the flux of substrates through the electron transport chain (ETC) can result in the generation of oxygen free radicals. Fortunately, several mechanisms exist to buffer bursts of intracellular ROS and peroxide production, including the enzymes Catalase, Glutathione Peroxidase and Superoxide Dismutase (SOD). Of the latter there are two intracellular isoforms; SOD1 which is mostly cytoplasmic, and SOD2 which is found exclusively in the mitochondria. Developmental and chronic loss of these enzymes has been linked to disease in several studies, however the temporal effects of these disturbances remain largely unexplored. Here, we induced a post-developmental (8-week old mice) deletion of SOD2 in skeletal muscle (SOD2-iMKO) and demonstrate that 16 weeks of SOD2 deletion leads to no major impairment in whole body metabolism, despite these mice displaying alterations in aspects of mitochondrial abundance and voluntary ambulatory movement. Furthermore, we demonstrated that SOD2 deletion impacts on specific aspects of muscle lipid metabolism, including the abundance of phospholipids and phosphatidic acid (PA), the latter being a key intermediate in several cellular signaling pathways. Thus, our findings suggest that post-developmental deletion of SOD2 induces a more subtle phenotype than previous embryonic models have shown, allowing us to highlight a previously unrecognized link between SOD2, mitochondrial function and bioactive lipid species including PA.

Skeletal muscle thermogenesis enables aquatic life in the smallest marine mammal

Science ◽  
2021 ◽  
Vol 373 (6551) ◽  
pp. 223-225
Author(s):  
Traver Wright ◽  
Randall W. Davis ◽  
Heidi C. Pearson ◽  
Michael Murray ◽  
Melinda Sheffield-Moore
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Rate ◽  
Basal Metabolic Rate ◽  
Tissue Level ◽  
Whole Body ◽  
Sea Otter ◽  
Aquatic Life ◽  
Respiratory Capacity ◽  
Metabolic Remodeling ◽  
Whole Body Metabolism

Basal metabolic rate generally scales with body mass in mammals, and variation from predicted levels indicates adaptive metabolic remodeling. As a thermogenic adaptation for living in cool water, sea otters have a basal metabolic rate approximately three times that of the predicted rate; however, the tissue-level source of this hypermetabolism is unknown. Because skeletal muscle is a major determinant of whole-body metabolism, we characterized respiratory capacity and thermogenic leak in sea otter muscle. Compared with that of previously sampled mammals, thermogenic muscle leak capacity was elevated and could account for sea otter hypermetabolism. Muscle respiratory capacity was modestly elevated and reached adult levels in neonates. Premature metabolic development and high leak rate indicate that sea otter muscle metabolism is regulated by thermogenic demand and is the source of basal hypermetabolism.

scholarly journals Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristine Williams ◽  
Lars R. Ingerslev ◽  
Jette Bork-Jensen ◽  
Martin Wohlwend ◽  
Ann Normann Hansen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Whole Body ◽  
Whole Body Metabolism

Activation of mTORC1 in skeletal muscle regulates whole-body metabolism through FGF21

2015 ◽  
Vol 8 (402) ◽  
pp. ra113-ra113 ◽  
Author(s):  
Maitea Guridi ◽  
Lionel A. Tintignac ◽  
Shuo Lin ◽  
Barbara Kupr ◽  
Perrine Castets ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Whole Body ◽  
Whole Body Metabolism

scholarly journals Rapid development of systemic insulin resistance with overeating is not accompanied by robust changes in skeletal muscle glucose and lipid metabolism

2013 ◽  
Vol 38 (5) ◽  
pp. 512-519 ◽  
Author(s):  
Andrea S. Cornford ◽  
Alexander Hinko ◽  
Rachael K. Nelson ◽  
Ariel L. Barkan ◽  
Jeffrey F. Horowitz
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Lipid Accumulation ◽  
Rapid Development ◽  
Insulin Response ◽  
Whole Body ◽  
Muscle Lipid ◽  
Wet Weight

Prolonged overeating and the resultant weight gain are clearly linked with the development of insulin resistance and other cardiometabolic abnormalities, but adaptations that occur after relatively short periods of overeating are not completely understood. The purpose of this study was to characterize metabolic adaptations that may accompany the development of insulin resistance after 2 weeks of overeating. Healthy, nonobese subjects (n = 9) were admitted to the hospital for 2 weeks, during which time they ate ∼4000 kcals·day−1 (70 kcal·kg−1 fat free mass·day−1). Insulin sensitivity was estimated during a meal tolerance test, and a muscle biopsy was obtained to assess muscle lipid accumulation and protein markers associated with insulin resistance, inflammation, and the regulation of lipid metabolism. Whole-body insulin sensitivity declined markedly after 2 weeks of overeating (Matsuda composite index: 8.3 ± 1.3 vs. 4.6 ± 0.7, p < 0.05). However, muscle markers of insulin resistance and inflammation (i.e., phosphorylation of IRS-1-Ser312, Akt-Ser473, and c-Jun N-terminal kinase) were not altered by overeating. Intramyocellular lipids tended to increase after 2 weeks of overeating (triacylglyceride: 7.6 ± 1.6 vs. 10.0 ± 1.8 nmol·mg−1 wet weight; diacylglyceride: 104 ± 10 vs. 142 ± 23 pmol·mg−1 wet weight) but these changes did not reach statistical significance. Overeating induced a 2-fold increase in 24-h insulin response (area under the curve (AUC); p < 0.05), with a resultant ∼35% reduction in 24-h plasma fatty acid AUC (p < 0.05). This chronic reduction in circulating fatty acids may help explain the lack of a robust increase in muscle lipid accumulation. In summary, our findings suggest alterations in skeletal muscle metabolism may not contribute meaningfully to the marked whole-body insulin resistance observed after 2 weeks of overeating.

scholarly journals Nutritional influences on age-related skeletal muscle loss

2013 ◽  
Vol 73 (1) ◽  
pp. 16-33 ◽  
Author(s):  
Ailsa A. Welch
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Fruits And Vegetables ◽  
Muscle Metabolism ◽  
Ubiquitin Proteasome System ◽  
Whole Body ◽  
Muscle Loss ◽  
Age Related ◽  
Anti Oxidant ◽  
Whole Body Metabolism

Age-related muscle loss impacts on whole-body metabolism and leads to frailty and sarcopenia, which are risk factors for fractures and mortality. Although nutrients are integral to muscle metabolism the relationship between nutrition and muscle loss has only been extensively investigated for protein and amino acids. The objective of the present paper is to describe other aspects of nutrition and their association with skeletal muscle mass. Mechanisms for muscle loss relate to imbalance in protein turnover with a number of anabolic pathways of which the mechanistic TOR pathway and the IGF-1–Akt–FoxO pathways are the most characterised. In terms of catabolism the ubiquitin proteasome system, apoptosis, autophagy, inflammation, oxidation and insulin resistance are among the major mechanisms proposed. The limited research associating vitamin D, alcohol, dietary acid–base load, dietary fat and anti-oxidant nutrients with age-related muscle loss is described. Vitamin D may be protective for muscle loss; a more alkalinogenic diet and diets higher in the anti-oxidant nutrients vitamin C and vitamin E may also prevent muscle loss. Although present recommendations for prevention of sarcopenia focus on protein, and to some extent on vitamin D, other aspects of the diet including fruits and vegetables should be considered. Clearly, more research into other aspects of nutrition and their role in prevention of muscle loss is required.

scholarly journals Action of GH on skeletal muscle function: molecular and metabolic mechanisms

2013 ◽  
Vol 52 (1) ◽  
pp. R107-R123 ◽  
Author(s):  
Viral Chikani ◽  
Ken K Y Ho
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
The Elderly ◽  
Energy System ◽  
Muscle Performance ◽  
Whole Body ◽  
Target Tissue ◽  
Dependent Manner ◽  
Skeletal Muscle Function ◽  
Body Protein

Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports and muscle function in the elderly. This paper critically reviews information on the effects of GH on muscle function covering structure, protein metabolism, the role of IGF1 mediation, bioenergetics and performance drawn from molecular, cellular and physiological studies on animals and humans. GH increases muscle strength by enhancing muscle mass without affecting contractile force or fibre composition type. GH stimulates whole-body protein accretion with protein synthesis occurring in muscular and extra-muscular sites. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. GH exerts complex multi-system effects on skeletal muscle function in part mediated by the IGF system.

scholarly journals Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Gagandeep Mann ◽  
Stephen Mora ◽  
Glory Madu ◽  
Olasunkanmi A. J. Adegoke
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Chronic Diseases ◽  
Branched Chain Amino Acids ◽  
Whole Body ◽  
Management Options ◽  
Impaired Metabolism ◽  
Whole Body Metabolism ◽  
Branched Chain ◽  
The Impact

Branched-chain amino acids (BCAAs) are critical for skeletal muscle and whole-body anabolism and energy homeostasis. They also serve as signaling molecules, for example, being able to activate mammalian/mechanistic target of rapamycin complex 1 (mTORC1). This has implication for macronutrient metabolism. However, elevated circulating levels of BCAAs and of their ketoacids as well as impaired catabolism of these amino acids (AAs) are implicated in the development of insulin resistance and its sequelae, including type 2 diabetes, cardiovascular disease, and of some cancers, although other studies indicate supplements of these AAs may help in the management of some chronic diseases. Here, we first reviewed the catabolism of these AAs especially in skeletal muscle as this tissue contributes the most to whole body disposal of the BCAA. We then reviewed emerging mechanisms of control of enzymes involved in regulating BCAA catabolism. Such mechanisms include regulation of their abundance by microRNA and by post translational modifications such as phosphorylation, acetylation, and ubiquitination. We also reviewed implications of impaired metabolism of BCAA for muscle and whole-body metabolism. We comment on outstanding questions in the regulation of catabolism of these AAs, including regulation of the abundance and post-transcriptional/post-translational modification of enzymes that regulate BCAA catabolism, as well the impact of circadian rhythm, age and mTORC1 on these enzymes. Answers to such questions may facilitate emergence of treatment/management options that can help patients suffering from chronic diseases linked to impaired metabolism of the BCAAs.

scholarly journals Vitamin D Merging into Immune System-Skeletal Muscle Network: Effects on Human Health

2020 ◽  
Vol 10 (16) ◽  
pp. 5592
Author(s):  
Clara Crescioli
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Immune System ◽  
Human Health ◽  
Hypovitaminosis D ◽  
Vitamin D Supplementation ◽  
Whole Body ◽  
Protective Effects ◽  
Skeletal Muscle Function ◽  
Vitamin D Levels

The concept that extra-skeletal functions of vitamin D impact on human health have taken place since quite ago. Among all, the beneficial effects of vitamin D on immune regulation, skeletal muscle function, and metabolism are undeniable. Adequate vitamin D levels maintain the immune system and skeletal muscle metabolism integrity, promoting whole-body homeostasis; hypovitaminosis D associates with the important decline of both tissues and promotes chronic inflammation, which is recognized to underlie several disease developments. Growing evidence shows that the immune system and skeletal muscle reciprocally dialogue, modulating each other’s function. Within this crosstalk, vitamin D seems able to integrate and converge some biomolecular signaling towards anti-inflammatory protective effects. Thus, vitamin D regulation appears even more critical at the immune system-muscle signaling intersection, rather than at the single tissue level, opening to wider/newer opportunities in clinical applications to improve health. This paper aims to focus on the immune system-skeletal muscle interplay as a multifaceted target for vitamin D in health and disease after recalling the main regulatory functions of vitamin D on those systems, separately. Some myokines, particularly relevant within the immune system/skeletal muscle/vitamin D networking, are discussed. Since vitamin D supplementation potentially offers the opportunity to maintain health, comments on this issue, still under debate, are included.

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