Dataset Information

Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men.

ABSTRACT:

Background

Skeletal muscle fat infiltration (myosteatosis) increases with aging, and has been associated with poor metabolic and musculoskeletal health, independent of overall adiposity. Studies examining the relationship of myosteatosis and mortality among older individuals recruited without regard to their health status are sparse.

Methods

We evaluated the association of peripheral computed tomography measured calf myosteatosis (intermuscular fat and muscle density as a measure of intramuscular fat) with mortality in 1,063 community-dwelling older men. Cox proportional hazards models were used to estimate the risk of mortality independent of potential confounders.

Results

During a mean follow-up of 7.2 years, 317 participants died. After adjustment for potential covariates and additional adjustment for whole body fat, lower skeletal muscle density was associated with increased all-cause mortality and cardiovascular disease mortality (hazard ratio [95% confidence interval] per standard deviation lower skeletal muscle density: 1.24 [1.09-1.41] and 1.46 [1.15-1.86], respectively), and to some extent with noncardiovascular disease mortality (1.18 [1.0-1.38], p = .053). After adjusting for trunk fat in a separate multivariable model, the association between skeletal muscle density and all-cause and cardiovascular disease mortality remained significant (both p < .01), while its association with noncardiovascular disease mortality became of borderline significance (p = .085). No other measures of adiposity, including calf intermuscular fat, were associated with mortality.

Conclusion

Our study reveals an independent association between skeletal muscle density and mortality in a community-based sample of older, predominantly Caucasian men. Further studies are needed to establish if this association is independent of other ectopic fat depots, and to identify the biological mechanisms underlying this relationship.

SUBMITTER: Miljkovic I

PROVIDER: S-EPMC4553718 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men.

Miljkovic Iva I Kuipers Allison L AL Cauley Jane A JA Prasad Tanushree T Lee Christine G CG Ensrud Kristine E KE Cawthon Peggy M PM Hoffman Andrew R AR Dam Thuy-Tien TT Gordon Christopher L CL Zmuda Joseph M JM

The journals of gerontology. Series A, Biological sciences and medical sciences 20150402 9

<h4>Background</h4>Skeletal muscle fat infiltration (myosteatosis) increases with aging, and has been associated with poor metabolic and musculoskeletal health, independent of overall adiposity. Studies examining the relationship of myosteatosis and mortality among older individuals recruited without regard to their health status are sparse.<h4>Methods</h4>We evaluated the association of peripheral computed tomography measured calf myosteatosis (intermuscular fat and muscle density as a measure ...[more]

PMID: 25838547

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Project description:BackgroundAgeing is accompanied by sarcopenia and intramuscular fat (IMAT) infiltration. In skeletal muscle, fat infiltration is a common feature in several myopathies and is associated with muscular dysfunction and insulin resistance. However, the cellular origin and lipidomic and transcriptomic changes during fat infiltration in skeletal muscle remain unclear.MethodsIn the current study, we generated a high IMAT-infiltrated skeletal muscle model by glycerol (GLY) injection. Single-cell RNA sequencing and lineage tracing were performed on GLY-injured skeletal muscle at 5 days post-injection (DPI) to identify the cell origins and dynamics. Lipidomics and RNA sequencing were performed on IMAT-infiltrated skeletal muscle at 14 DPI (or 17 DPI for the cold treatment) to analyse alterations of lipid compositions and gene expression levels.ResultsWe identified nine distinct major clusters including myeloid-derived cells (52.13%), fibroblast/fibro/adipogenic progenitors (FAPs) (23.24%), and skeletal muscle stem cells (2.02%) in GLY-injured skeletal muscle. Clustering and pseudotemporal trajectories revealed six subpopulations in fibroblast/FAPs and 10 subclusters in myeloid-derived cells. A subpopulation of myeloid-derived cells expressing adipocyte-enriched genes and Pdgfra- /Cd68+ cells displayed lipid droplets upon adipogenic induction, indicating their adipogenic potential. Lipidomic analysis revealed the changes of overall lipid classes composition (e.g. triglycerides (TAGs) increased by 19.3 times, P = 0.0098; sulfoquinovosyl diacylglycerol decreased by 83%, P = 0.0056) and in the distribution of lipids [e.g. TAGs (18:2/18:2/22:6) increased by 181.6 times, P = 0.021] between GLY-group and saline control. RNA-seq revealed 1847 up-regulated genes and 321 down-regulated genes and significant changes in lipid metabolism-related pathways (e.g. glycerolipid pathway and glycerophospholipid pathway) in our model of GLY-injured skeletal muscle. Notably, short-term cold exposure altered fatty acid composition (e.g. saturated fatty acid decreased by 6.4%, P = 0.058) in fat-infiltrated muscles through directly affecting lipid metabolism pathways including PI3K-AKT and MAPK signalling pathway.ConclusionsOur results showed that a subpopulation of myeloid-derived cells may contribute to IMAT infiltration. GLY-induced IMAT infiltration changed the lipid composition and gene expression profiles. Short-term cold exposure might regulate lipid metabolism and its related signalling pathways in fat-infiltrated muscle. Our study provides a comprehensive resource describing the molecular signature of fat infiltration in skeletal muscle.

Dataset Information

Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men.

Background

Methods

Results

Conclusion

Publications

Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men.

Similar Datasets

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