Muscle Quality and Myosteatosis: Novel Associations With Mortality Risk

Reinders, Ilse; Murphy, Rachel A.; Brouwer, Ingeborg A.; Visser, Marjolein; Launer, Lenore J.; Siggeirsdóttir, Kristín; Eiríksdóttir, Guðný; Gudnason, Vilmundur; Jónsson, Pálmi V.; Lang, Thomas; Harris, Tamara B.

doi:10.1093/aje/kwv153

Cited by 120 publications

(56 citation statements)

References 40 publications

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“…Aging in humans is accompanied by a loss of subcutaneous fat but an accumulation of AC and lipids in non-adipose depots, such as bone marrow, liver, and skeletal muscle ( 2 ). Fatty infiltration of skeletal muscle (myosteatosis) has, in particular, been recognized as an important component of aging and frailty ( 21 – 26 ). Lipid accumulation in muscles of the lower limb is also associated with increased fracture risk in the elderly ( 27 ).…”

Section: Fatty Infiltration In Skeletal Muscle: Cellular and Moleculamentioning

confidence: 99%

Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity

2016

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Skeletal muscle and bone share common embryological origins from mesodermal cell populations and also display common growth trajectories early in life. Moreover, muscle and bone are both mechanoresponsive tissues, and the mass and strength of both tissues decline with age. The decline in muscle and bone strength that occurs with aging is accompanied in both cases by an accumulation of adipose tissue. In bone, adipocyte (AC) accumulation occurs in the marrow cavities of long bones and is known to increase with estrogen deficiency, mechanical unloading, and exposure to glucocorticoids. The factors leading to accumulation of intra- and intermuscular fat (myosteatosis) are less well understood, but recent evidence indicates that increases in intramuscular fat are associated with disuse, altered leptin signaling, sex steroid deficiency, and glucocorticoid treatment, factors that are also implicated in bone marrow adipogenesis. Importantly, accumulation of ACs in skeletal muscle and accumulation of intramyocellular lipid are linked to loss of muscle strength, reduced insulin sensitivity, and increased mortality among the elderly. Resistance exercise and whole body vibration can prevent fatty infiltration in skeletal muscle and also improve muscle strength. Therapeutic strategies to prevent myosteatosis may improve muscle function and reduce fall risk in the elderly, potentially impacting the incidence of bone fracture.

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Section: Fatty Infiltration In Skeletal Muscle: Cellular and Moleculamentioning

confidence: 99%

Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity

2016

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“…The main consequence is reduced muscle protein synthesis, which also depends on ultrastructural modifications in the number and functionality of mitochondria and intracellular lipid deposition [ 12 , 13 ]. Anabolic resistance also promotes adipose infiltration in the muscle, which contributes to decreased muscle functionality [ 14 , 15 ].…”

Section: Introduction: Sarcopenia and Physical Frailty In Agingmentioning

confidence: 99%

Aging Gut Microbiota at the Cross-Road between Nutrition, Physical Frailty, and Sarcopenia: Is There a Gut–Muscle Axis?

et al. 2017

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Inadequate nutrition and physical inactivity are the mainstays of primary sarcopenia–physiopathology in older individuals. Gut microbiota composition is strongly dependent on both of these elements, and conversely, can also influence the host physiology by modulating systemic inflammation, anabolism, insulin sensitivity, and energy production. The bacterial metabolism of nutrients theoretically influences skeletal muscle cell functionality through producing mediators that drive all of these systemic effects. In this study, we review the scientific literature supporting the concept of the involvement of gut microbiota in primary sarcopenia physiopathology. First, we examine studies associating fecal microbiota alterations with physical frailty, i.e., the loss of muscle performance and normal muscle mass. Then, we consider studies exploring the effects of exercise on gut microbiota composition. Finally, we examine studies demonstrating the possible effects of mediators produced by gut microbiota on skeletal muscle, and intervention studies considering the effects of prebiotic or probiotic administration on muscle function. Even if there is no evidence of a distinct gut microbiota composition in older sarcopenic patients, we conclude that the literature supports the possible presence of a “gut–muscle axis”, whereby gut microbiota may act as the mediator of the effects of nutrition on muscle cells.

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“…Muscle fatty infiltration is closely associated with muscle atrophy, inflammation, insulin resistance, mobility impairments, fracture, and even mortality in the elderly 14, 15, 16, 17. Although the factors leading to fat accumulation in the muscle are not yet fully defined, it has been reported that aging, muscle injury, mechanical unloading, and hormonal imbalance are main causes of ectopic fat formation 1, 2, 18, 19, 20.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

Lee

Kim

et al. 2017

J cachexia sarcopenia muscle

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BackgroundFatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid‐binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model.MethodsIn the RCT model, we evaluated the expression of FABP4 by qRT‐PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia‐inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively.ResultsFABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear‐induced FABP4 expression was up‐regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter activity of FABP4, together with HIF1β. Hypoxia‐induced FABP4 expression was significantly decreased by HIF1 inhibitor treatment. Furthermore, in RCT model mice, fat accumulation was remarkably reduced by FABP4 inhibitor treatment.ConclusionsThis study shows that RCT induces FABP4 expression, leading to fat accumulation in injured muscle. FABP4 transcription is regulated by the direct binding of HIF1 to the FABP4 promoter in the hypoxic condition induced by RCT. Fat accumulation in injured muscle was reduced by the inhibition of FABP4. Ultimately, in the RCT model, we identified a novel mechanism for fatty infiltration by FABP4, which differs from adipogenic differentiation of muscle stem cells, and we found that fatty infiltration might be regulated by inhibition of HIF1 or FABP4.

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Muscle Quality and Myosteatosis: Novel Associations With Mortality Risk

Cited by 120 publications

References 40 publications

Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity

Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity

Aging Gut Microbiota at the Cross-Road between Nutrition, Physical Frailty, and Sarcopenia: Is There a Gut–Muscle Axis?

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

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