Intramyocellular Lipid and Impaired Myofiber Contraction in Normal Weight and Obese Older Adults

Choi, Si–Kyung; Files, D. Clark; Zhang, Tan; Wang, Zhongmin; Messi, Marı́a Laura; Gregory, Heather; Stone, John Van; Lyles, Mary F.; Dhar, Sanjay; Marsh, Anthony P.; Nicklas, Barbara J.; Delbono, Osvaldo

doi:10.1093/gerona/glv169

Cited by 143 publications

(175 citation statements)

References 32 publications

(32 reference statements)

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“…This finding, along with the lack of reduced muscle mass at day 10, suggest that atrophy does not account for the loss of muscle function in old mice at day 10. Further histological evaluation of soleus muscle in ALI mice revealed increased intramyocellular lipid (IMCL) droplet size in old versus young ALI mice at day 10 in both type I and type II myofibers (Figure 1K), a finding associated with both impaired skeletal muscle function (Choi et al 2016; Picard et al 2012) and metabolism (Consitt et al 2009) in previous studies.…”

Section: Resultssupporting

confidence: 52%

“…While the mechanistic link between the metabolic changes seen in old mouse muscle and the reduction in muscle contractile force are not fully elucidated in this study, we find increased size of intramyocellular lipid droplets in old ALI muscle at day 10. Other studies have found an association between intramyocellular lipid accumulation and impaired muscle contractility in mice and humans (Choi et al 2016; Duval et al 2007; Picard et al 2012; Pugh et al 2013), though the mechanisms underlying this association remain unclear.…”

Section: Discussionmentioning

confidence: 94%

“…Soleus muscle lipid content was identified on serial sections, using the Oil Red O (Poly Scientific R&D) staining method. Lipid droplet size measurements were obtained in at least 20 myofibers per muscle section and quantified using Image J® software (NIH, Bethesda MD) as previously described (Choi et al 2016). …”

Section: Methodsmentioning

confidence: 99%

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Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

et al. 2016

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Introduction Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more clinically significant in older persons. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung injury-induced skeletal muscle atrophy in young mice and identify an alternative role for MuRF1 in cardiac metabolism regulation through inhibition of fatty acid oxidation. Objectives To develop a model of lung injury-induced muscle wasting in old mice and to evaluate the skeletal muscle metabolomic profile of adult and old acute lung injury (ALI) mice. Methods Young (2 month), adult (6 month) and old (20 month) male C57Bl6J mice underwent Sham (intratracheal H2O) or ALI [intratracheal E. coli lipopolysaccharide (i.t. LPS)] conditions and muscle functional testing. Metabolomic analysis on gastrocnemius muscle was performed using gas chromatography-mass spectrometry (GC-MS). Results Old ALI mice had increased mortality and failed to recover skeletal muscle function compared to adult ALI mice. Muscle MuRF1 expression was increased in old ALI mice at day 3. Non-targeted muscle metabolomics revealed alterations in amino acid biosynthesis and fatty acid metabolism in old ALI mice. Targeted metabolomics of fatty acid intermediates (acyl-carnitines) and amino acids revealed a reduction in long chain acyl-carnitines in old ALI mice. Conclusion This study demonstrates age-associated susceptibility to ALI-induced muscle wasting which parallels a metabolomic profile suggestive of altered muscle fatty acid metabolism. MuRF1 activation may contribute to both atrophy and impaired fatty acid oxidation, which may synergistically impair muscle function in old ALI mice.

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Section: Resultssupporting

confidence: 52%

Section: Discussionmentioning

confidence: 94%

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Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

et al. 2016

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“…Undernutrition is a powerful risk factor for sarcopenia (4,23) and might well explain the increased prevalence of sarcopenia in patients with lower BMI levels. On the other hand, although sarcopenia often coexists with elevated BMI, a condition referred to as sarcopenic obesity (24), it has been demonstrated that compared to normal weight individuals, obese subjects have greater thigh muscle volume, increased crosssectional area of type I skeletal muscle fibers, increased muscle lipid content (25), and a lower muscle quality (26).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Clinical Correlates of Sarcopenia, Identified According to the EWGSOP Definition and Diagnostic Algorithm, in Hospitalized Older People: The GLISTEN Study

Bianchi

Abete

Bellelli

et al. 2017

The Journals of Gerontology: Series A

111

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Background: Prevalence of sarcopenia is substantial in most geriatrics settings, but estimates vary greatly across studies because of difference in population characteristics, diagnostic criteria, and methods used to assess muscle mass, muscle strength, and physical performance. We investigated the feasibility of the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm assessment in hospitalized older adults and analyzed prevalence and clinical correlates of sarcopenia. Methods: Cross-sectional analysis of 655 participants enrolled in a multicenter observational study of older adults admitted to 12 acute hospital wards in Italy. Sarcopenia was assessed as low skeletal mass index (kg/m 2 ) plus either low handgrip strength or low walking speed (EWGSOP criteria). Skeletal muscle mass was estimated using bioimpedance analysis. Results: Of the 655 patients (age 81.0 ± 6.8 years; women 51.9%) enrolled in the study, 275 (40.2%) were not able to perform the 4-m walking test because of medical problems. The overall prevalence of sarcopenia on hospital admission was 34.7% (95% confidence interval 28-37) and it steeply increased with aging (p < .001). In multivariable analysis, patients with sarcopenia on hospital admission were older and were more likely to be male and to have congestive heart failure, cerebrovascular disease, and severe basic activities of daily living disability. The prevalence of sarcopenia was inversely correlated with body mass index.

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“…Intramyocellular lipid and ectopic adipocytes are found in a range of conditions with decreased muscle mass and strength, including aged muscle, 98 disuse, 99 and muscular dystrophies, such as Duchene muscular dystrophy (DMD). 100 Fatty muscle has also been identified in the pathogenesis of obesity 101 and linked to poor muscular mechanical properties 102 and insulin resistance. 103 Importantly, myosteatosis accelerates with age, and fatty infiltration in the thigh muscle is associated with increased risk of hip fracture in the elderly.…”

Section: Impact Of Obesity On Musculoskeletal Tissue Systemsmentioning

confidence: 99%

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity

Frechette

Krishnamoorthy

Pamon

et al. 2017

Annals of the New York Academy of Sciences

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The incidence of obesity is rapidly rising, increasing morbidity and mortality rates worldwide. Associated comorbidities include type 2 diabetes, heart disease, fatty liver disease, and cancer. The impact of excess fat on musculoskeletal health is still unclear, although it is associated with increased fracture risk and a decline in muscular function. The complexity of obesity makes understanding the etiology of bone and muscle abnormalities difficult. Exercise is an effective and commonly prescribed non-pharmacological treatment option, but it can be difficult or unsafe for the frail, elderly, and morbidly obese. Exercise alternatives, such as low-intensity vibration (LIV), have potential for improving musculoskeletal health, particularly in conditions with excess fat. LIV has been shown to influence bone marrow mesenchymal stem cell differentiation toward higher-order tissues (i.e., bone) and away from fat. While the exact mechanisms are not fully understood, recent studies utilizing LIV both at the bench and in the clinic have demonstrated its efficacy. Here, we discuss the current literature investigating the effects of obesity on bone, muscle, and bone marrow and how exercise and LIV can be used as effective treatments for combating the negative effects in the presence of excess fat.

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Intramyocellular Lipid and Impaired Myofiber Contraction in Normal Weight and Obese Older Adults

Abstract: These data indicate that greater intramyocellular lipids are associated with slower myofiber contraction, force, and power development in obese older adults.

Cited by 143 publications

References 32 publications

Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

Prevalence and Clinical Correlates of Sarcopenia, Identified According to the EWGSOP Definition and Diagnostic Algorithm, in Hospitalized Older People: The GLISTEN Study

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity

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