ULK1 and ULK2 modulate skeletal muscle homeostasis and whole-body metabolism

2020 ◽  
Author(s):  
Jordan D Fuqua
Keyword(s):  
Skeletal Muscle ◽  
Whole Body ◽  
Whole Body Metabolism ◽  
Muscle Homeostasis

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 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 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 Alterations to mTORC1 signaling in the skeletal muscle differentially affect whole-body metabolism

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Maitea Guridi ◽  
Barbara Kupr ◽  
Klaas Romanino ◽  
Shuo Lin ◽  
Denis Falcetta ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Whole Body ◽  
Mtorc1 Signaling ◽  
Whole Body Metabolism

Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine

2014 ◽  
Vol 306 (5) ◽  
pp. E469-E482 ◽  
Author(s):  
Susanne Keipert ◽  
Mario Ost ◽  
Kornelia Johann ◽  
Francine Imber ◽  
Martin Jastroch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Uncoupling Protein ◽  
Ectopic Expression ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Fibroblast Growth Factor 21 ◽  
Mitochondrial Uncoupling ◽  
Whole Body Metabolism

UCP1-Tg mice with ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) are a model of improved substrate metabolism and increased longevity. Analysis of myokine expression showed an induction of fibroblast growth factor 21 (FGF21) in SM, resulting in approximately fivefold elevated circulating FGF21 in UCP1-Tg mice. Despite a reduced muscle mass, UCP1-Tg mice showed no evidence for a myopathy or muscle autophagy deficiency but an activation of integrated stress response (ISR; eIF2α/ATF4) in SM. Targeting mitochondrial function in vitro by treating C2C12 myoblasts with the uncoupler FCCP resulted in a dose-dependent activation of ISR, which was associated with increased expression of FGF21, which was also observed by treatment with respiratory chain inhibitors antimycin A and myxothiazol. The cofactor required for FGF21 action, β-klotho, was expressed in white adipose tissue (WAT) of UCP1-Tg mice, which showed an increased browning of WAT similar to what occurred in altered adipocyte morphology, increased brown adipocyte markers (UCP1, CIDEA), lipolysis (HSL phosphorylation), and respiratory capacity. Importantly, treatment of primary white adipocytes with serum of transgenic mice resulted in increased UCP1 expression. Additionally, UCP1-Tg mice showed reduced body length through the suppressed IGF-I-GH axis and decreased bone mass. We conclude that the induction of FGF21 as a myokine is coupled to disturbance of mitochondrial function and ISR activation in SM. FGF21 released from SM has endocrine effects leading to increased browning of WAT and can explain the healthy metabolic phenotype of UCP1-Tg mice. These results confirm muscle as an important endocrine regulator of whole body metabolism.

scholarly journals Signals from the Circle: Tricarboxylic Acid Cycle Intermediates as Myometabokines

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 474
Author(s):  
Jennifer Maurer ◽  
Miriam Hoene ◽  
Cora Weigert
Keyword(s):  
Skeletal Muscle ◽  
Tricarboxylic Acid Cycle ◽  
Cell Types ◽  
Tricarboxylic Acid ◽  
Muscle Performance ◽  
Whole Body ◽  
Small Proteins ◽  
Exercise Adaptation ◽  
Whole Body Metabolism ◽  
Adaptation Processes

Regular physical activity is an effective strategy to prevent and ameliorate aging-associated diseases. In particular, training increases muscle performance and improves whole-body metabolism. Since exercise affects the whole organism, it has countless health benefits. The systemic effects of exercise can, in part, be explained by communication between the contracting skeletal muscle and other organs and cell types. While small proteins and peptides known as myokines are the most prominent candidates to mediate this tissue cross-talk, recent investigations have paid increasing attention to metabolites. The purpose of this review is to highlight the potential role of tricarboxylic acid (TCA) metabolites as humoral mediators of exercise adaptation processes. We focus on TCA metabolites that are released from human skeletal muscle in response to exercise and provide an overview of their potential auto-, para- or endocrine health-promoting effects.

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.

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