Dataset Information

Greater skeletal muscle fat infiltration is associated with higher all-cause mortality among men of African ancestry.

ABSTRACT:

Background

fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations.

Methods

in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy.

Results

one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ?65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models.

Conclusions

our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship.

SUBMITTER: Zhao Q

PROVIDER: S-EPMC4916343 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Greater skeletal muscle fat infiltration is associated with higher all-cause mortality among men of African ancestry.

Zhao Qian Q Zmuda Joseph M JM Kuipers Allison L AL Jonnalagadda Pallavi P Bunker Clareann H CH Patrick Alan L AL Youk Ada O AO Miljkovic Iva I

Age and ageing 20160413 4

<h4>Background</h4>fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations.<h4>Methods</h4>in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis ...[more]

PMID: 27076522

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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 mortality among men of African ancestry.

Background

Methods

Results

Conclusions

Publications

Greater skeletal muscle fat infiltration is associated with higher all-cause mortality among men of African ancestry.

Similar Datasets

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