Plasma Metabolites Associated with Muscle Fat Infiltration in Community-Dwelling Older Adults from the Health ABC Study

Abstract

Abstract Objectives Age-related increase in muscle fat depots, i.e., myosteatosis, is a contributing factor to muscular dysfunction in older adults leading to frailty and disability. Myosteatosis is a complex condition that is associated with aging and diverse pathologies, including cancer and diabetes. We have previously shown that the relationship between muscle fat deposition and reduced physical function is moderated by muscle area and it is only observed in individuals with high muscle area. A further characterization of the metabolic phenotype associated with myoseatosis may shed light on the underlying biological mechanisms involved in its pathophysiology. Thus, we sought to further explore the heterogeneity of myosteatosis using a semi-targeted metabolomics approach to determine the plasma metabolites associated with myosteatosis in community-dwelling older men. Methods We performed a cross-sectional analysis of 314 African-American men (age: 69–79 years) from the Health ABC study at baseline. Mid-thigh inter-muscular fat (IMF) area by CT and 350 plasma metabolites by liquid-chromatography/mass spectrometry were measured. Partial correlation analysis was performed to determine metabolites associated with IMF. Results 161 metabolites were correlated with IMF (P < 0.05). After adjustment for age, weight, physical activity, medications and smoking, 36 metabolites remained significant with a false discovery rate of ≤0.25 to correct for multiple comparisons. Majority of IMF-associated metabolites were lipids/lipid-like molecules (26/36), followed by organic acids, including amino acids (5/36). Among these metabolites, only glutamine (from organic-acids) and mevalonic acid, (from fatty acids) were negatively correlated with IMF, while the remaining 34 metabolites were positively correlated. Notably, metabolic profiles of participants were distinctly different across different levels of myosteatosis, categorized by quartiles of IMF. Conclusions Dysregulated lipid and amino acid metabolism was a metabolomic hallmark of myosteatosis in this cohort of older men. Further exploration of metabolic heterogeneity of myosteatosis may help better understand the significance of fat infiltration on muscle health in aging. Funding Sources NIH/National Institute of Aging & NIA T32-AG0001810.