Milazzo Laura, Menzaghi Barbara, Caramma Ilaria, Nasi Milena, Sangaletti Ornella, Cesari Miriam, Zanone Poma Barbara, Cossarizza Andrea, Antinori Spinello, Galli Massimo
Università degli Studi di Milano, Department of Clinical Sciences, L. Sacco Hospital, Section of Infectious Diseases and Immunopathology, Milan, Italy.
AIDS Res Hum Retroviruses. 2010 Nov;26(11):1207-14. doi: 10.1089/aid.2010.0024. Epub 2010 Oct 26.
We investigated the effect of antioxidant supplementation on mitochondrial function, fat distribution, and lipid and glucose metabolism in HIV-1-infected patients with antiretroviral therapy (ART)-related lipoatrophy. 61 ART-treated HIV-1-infected patients with lipoatrophy were randomized to receive either n-acetyl-L-carnitine (n = 21), lipoic acid + n-acetylcisteine (LA/NAC) (n = 20), or no supplementation (n = 20) for 48 weeks. At baseline and at the end of treatment, mitochondrial function was studied by (13)C-methionine breath test and by mitochondrial (mt)-DNA quantification on circulating T-cells and subcutaneous adipose tissue. Body composition was assessed by dual-energy X-ray absorpiometry (DEXA). (13)CO(2)-exhalation increased between baseline and week 48 in both supplementation arms as evidenced by a higher delta over baseline excretion at 45 min (from mean ± SEM of 7.8 ± 1.08 to 9.9 ± 0.6, p = 0.04 in the n-acetyl-carnitine arm, and from 7.4 ± 0.8 to 11.5 ± 1.6, p = 0.01 in LA/NAC arm). Cumulative (13)CO2 excretion increased from median (interquartile range; IQR) of 3.25 (2.55-4.2) to 4.51 (4.12-5.2) in the carnitine arm; from 3.79 (2.67-4.37) to 4.83 (4.25-5.56) in the LA/NAC arm; p = 0.004, 0.02, respectively. mtDNA content increased in CD4+ T-cells from patients who received n-acetyl-carnitine (+30 copies/cell; p = 0.03), without significant difference by the overall comparison of the study groups. Fat body mass and lipid profile did not change significantly in any of the arms. Our study showed that antioxidant supplementation may have a protective role on mitochondrial function, with limited effects on the reversal of clinical lipodystrophic abnormalities in HIV-1-infected patients.
我们研究了补充抗氧化剂对接受抗逆转录病毒疗法（ART）相关脂肪萎缩的HIV-1感染患者的线粒体功能、脂肪分布以及脂质和葡萄糖代谢的影响。61例接受ART治疗且患有脂肪萎缩的HIV-1感染患者被随机分为三组，分别接受n-乙酰-L-肉碱（n = 21）、硫辛酸 + n-乙酰半胱氨酸（LA/NAC）（n = 20）或不进行补充剂治疗（n = 20），为期48周。在基线和治疗结束时，通过（13）C-蛋氨酸呼气试验以及对循环T细胞和皮下脂肪组织进行线粒体（mt）-DNA定量来研究线粒体功能。通过双能X线吸收法（DEXA）评估身体成分。两个补充剂治疗组在基线至第48周期间（13）CO₂呼出量均增加，45分钟时相对于基线排泄量的增量更高可证明这一点（n-乙酰肉碱组从平均±SEM的7.8±1.08增至9.9±0.6，p = 0.04；LA/NAC组从7.4±0.8增至11.5±1.6，p = 0.01）。肉碱组累积（13）CO₂排泄量从中位数（四分位间距；IQR）3.25（2.55 - 4.2）增至4.51（4.12 - 5.2）；LA/NAC组从3.79（2.67 - 4.37）增至4.83（4.25 - 5.56）；p分别为0.004、0.02。接受n-乙酰肉碱治疗患者的CD4⁺T细胞中线粒体DNA含量增加（+30拷贝/细胞；p = 0.03），但研究组总体比较无显著差异。任何一组的脂肪量和脂质谱均无显著变化。我们的研究表明，补充抗氧化剂可能对线粒体功能具有保护作用，但对HIV-1感染患者临床脂肪代谢障碍异常的逆转作用有限。
