Lipid modulation of skeletal muscle mass and function

Lipina, Christopher; Hundal, Harinder S.

doi:10.1002/jcsm.12144

Cited by 191 publications

(179 citation statements)

References 117 publications

(246 reference statements)

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“…Accumulation of intramuscular lipids plays a pathogenic role in insulin resistance and type 2 diabetes . Finally, several recent studies highlighted the involvement of fatty acids and their metabolites, such as DAG and ceramides, in blocking muscle growth and altering myofiber metabolism . For this reason, we investigated how the modulation of Plin2 expression could affect the lipid metabolites in adult skeletal muscle and whether this can account for the observed effect on myofiber size.…”

Section: Discussionmentioning

confidence: 95%

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Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy

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Armani

Conte

et al. 2018

J cachexia sarcopenia muscle

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Background Perilipin2 (Plin2) belongs to a family of five highly conserved proteins, known for their role in lipid storage. Recent data indicate that Plin2 has an important function in cell metabolism and is involved in several human pathologies, including liver steatosis and Type II diabetes. An association between Plin2 and lower muscle mass and strength has been found in elderly and inactive people, but its function in skeletal muscle is still unclear. Here, we addressed the role of Plin2 in adult muscle by gain and loss of function experiments. Methods By mean of in vivo Plin2 down‐regulation (shPlin2) and overexpression (overPlin2) in murine tibialis anterior muscle, we analysed the effects of Plin2 genetic manipulations on myofiber size and lipid composition. An analysis of skeletal muscle lipid composition was also performed in vastus lateralis samples from young and old patients undergoing hip surgery. Results We found that Plin2 down‐regulation was sufficient to induce a 30% increase of myofiber cross‐sectional area, independently of mTOR pathway. Alterations of lipid content and modulation of genes involved in lipid synthesis occurred in hypertrophic muscles. In particular, we showed a decrease of triglycerides, ceramides, and phosphatidylcoline:phosphatidylethanolamine ratio, a condition known to impact negatively on muscle function. Plin2 overexpression did not change fibre size; however, lipid composition was strongly affected in a way that is similar to that observed in human samples from old patients. Conclusions Altogether these data indicate that Plin2 is a critical mediator for the control of muscle mass, likely, but maybe not exclusively, through its critical role in the regulation of intracellular lipid content and composition.

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Section: Discussionmentioning

confidence: 95%

“…Skeletal muscle is another important player in lipid metabolism. In fact, intracellular accumulation of fatty acids has been reported to affect both muscle mass and function . The role of Plin2 in muscle physiopathology has not been yet dissected.…”

Section: Introductionmentioning

confidence: 99%

Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy

Conte

Armani

Conte

et al. 2018

J cachexia sarcopenia muscle

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“…Mechanisms mediating metabolic lipotoxicity are complex and appear to include direct pro-oxidative and inflammatory activities [28] as well as accumulation of metabolically toxic lipid moieties such as diacylglycerol and ceramides [34]. Recent evidences show that ectopic lipid deposition may also compromise muscle protein turnover [35].…”

Section: Introduction: What We Knowmentioning

confidence: 99%

Sarcopenic Obesity: Time to Meet the Challenge

et al. 2018

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The prevalence of overweight and obesity has reached epidemic proportions worldwide due to increasingly pervasive obesogenic lifestyle changes. Obesity poses unprecedented individual, social, and multidisciplinary medical challenges by increasing the risk for metabolic diseases, chronic organ failures, and cancer as well as complication rates in the presence of acute disease conditions. Whereas reducing excess adiposity remains the fundamental pathogenic treatment for obese individuals, complex metabolic and lifestyle abnormalities as well as weight reduction therapies per se may also compromise the ability to preserve muscle function and mass, especially when chronic disease co-exists with obesity. Emerging evidence indicates that low muscle mass and quality have a strong negative prognostic impact in obese individuals and may lead to frailty, disability, and increased morbidity and mortality. Awareness of the importance of skeletal muscle maintenance in obesity is however low among clinicians and scientists. The term ‘sarcopenic obesity' has been proposed to identify obesity with low skeletal muscle function and mass, but its utilization is largely limited to the aging patient population, and consensus on its definition and diagnostic criteria remains insufficient. Knowledge on prevalence of sarcopenic obesity in various clinical conditions and patient subgroups, on its clinical impacts in patient risk stratification, and on effective prevention and treatment strategies remain therefore dramatically inadequate. In particular, optimal dietary options and medical nutritional support strategies to preserve muscle mass in obese individuals remain largely undefined. The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) recognize and indicate obesity with altered body composition due to low skeletal muscle function and mass (sarcopenic obesity) as a scientific and clinical priority for researchers and clinicians. ESPEN and EASO therefore call for coordinated action aimed at reaching consensus on its definition, diagnostic criteria, and optimal treatment with particular regard to nutritional therapy. We are convinced that achievement of these goals has a strong potential to reduce the burden of morbidity and mortality in the rapidly increasing obese patient population.

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“…Sarcopenia can also be diagnosed by measuring the psoas muscle area (4,5). Although nutritional management of cancer patients to prevent and resolve sarcopenia has not been established, attention has been focused on the effects of fatty acid administration on cancer patients (6)(7)(8). Furthermore, studies that have identified a relationship between a significant decrease in psoas muscle volume and CRP increase in patients with cancer cachexia (9).…”

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confidence: 99%