Koethe John R, Robles Michelle E, Widmer Annaliese, Lillegard Kate, Fan Run, Liu Qi, Bailin Samuel, Silver Heidi J
Vanderbilt University Medical Center, Division of Infectious Diseases, Nashville, TN, USA.
Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, TN, USA.
AIDS. 2025 Jun 5. doi: 10.1097/QAD.0000000000004258.
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.
Cross-sectional analysis of two prospectively recruited clinical cohorts with harmonized study procedures and imaging.
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.
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.
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.
骨骼肌内过量脂质的蓄积会发展为明显的肌脂肪变性，在感染HIV者（PWH）中更为常见，并会导致身体虚弱、行动能力受损和代谢失调。过量的游离脂肪酸（FFA）会损害肌肉线粒体功能，这在几种酰基肉碱的血浆水平升高中有所体现。我们评估了长期接受抗逆转录病毒治疗的男性PWH中CT测定的骨骼肌密度与血浆酰基肉碱之间的关系。
对两个采用统一研究程序和成像方法的前瞻性招募临床队列进行横断面分析。
线性回归模型评估了通过液相色谱/质谱法测量的空腹血浆酰基肉碱与通过CT测量的骨骼肌密度之间的关系，并对研究队列、年龄、体重指数（BMI）、CD4 +细胞计数、内脏脂肪组织面积、总血浆甘油三酯和胰岛素抵抗进行了校正。
在160名男性PWH中（中位年龄54岁，中位BMI 30.5 kg/m²，41%为黑人），短链乙酰肉碱（C2:0）、异丁酰肉碱（C4:0）、中链己酰肉碱（C6:1）、长链肉豆蔻酰肉碱（C14:0）和棕榈酰肉碱（C16:0）的血浆水平升高与骨骼肌密度相关，而其他一些接近显著水平。主要作为支链氨基酸代谢产物的C3和C5酰基肉碱均与骨骼肌密度无关。
男性PWH骨骼肌密度的CT测量似乎可识别出由FFA代谢物测量的线粒体功能受损，这可作为未来干预研究的生物标志物，以减轻骨骼肌退化和代谢失调。
