Lower skeletal muscle density on CT imaging is associated with incomplete fatty acid oxidation, as measured by plasma acylcarnitines, in men with HIV.

Objective: The accumulation of excess lipids within skeletal muscle, which can progress to overt myosteatosis, is more common among persons with HIV (PWH) and contributes to the development of frailty, impaired mobility, and metabolic dysregulation. Excess free fatty acids (FFA) can impair muscle mitochondrial function, which is reflected in higher plasma levels of several acylcarnitines. We assessed the relationship between CT-determined skeletal muscle density and plasma acylcarnitines among male PWH on long-term antiretroviral therapy.

Design: Cross-sectional analysis of two prospectively recruited clinical cohorts with harmonized study procedures and imaging.

Methods: Linear regression models assessed the relationship of fasting plasma acylcarnitines measured by liquid chromatography/mass spectrometry and skeletal muscle density measured by CT, adjusted for study cohort, age, body mass index (BMI), CD4+ cell count, visceral adipose tissue area, total plasma triglycerides, and insulin resistance.

Results: Among 160 male PWH (median age 54 years, median BMI 30.5 kg/m2, and 41% Black), higher plasma levels of short-chain acetylcarnitine (C2:0) and isobutyrylcarnitine (C4:0), the medium chain hexanoylcarnitine (C6:1), and the long chain myristoylcarnitine (C14:0) and palmitoylcarnitine (C16:0) were associated with skeletal muscle density, while others approached significance. None of the C3 and C5 acylcarnitines, largely the products of branched-chain amino acid metabolism, were associated with skeletal muscle density.

Conclusions: CT measurements of skeletal muscle density in male PWH appear to identify impaired mitochondrial function as measured by FFA metabolites, which could serve as a biomarker for future intervention studies to mitigate skeletal muscle deterioration and metabolic dysregulation.