Luzi Livio, Perseghin Gianluca, Tambussi Giuseppe, Meneghini Elena, Scifo Paola, Pagliato Emanuela, Del Maschio Alessandro, Testolin Giulio, Lazzarin Adriano
International Center for Assessment of the Nutritional Status and Clinical Research Unit II, Universita' degli Studi di Milano, 20132 Milan, Italy.
Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E274-80. doi: 10.1152/ajpendo.00391.2001. Epub 2002 Oct 8.
Antiretroviral therapy in human immunodeficiency virus (HIV)-positive patients can induce a lipodystrophy syndrome of peripheral fat wasting and central adiposity, dyslipidemia, and insulin resistance. To test whether in this syndrome insulin resistance is associated with abnormal muscle handling of fatty acids, 12 HIV-1 patients (8 females/4 males, age = 26 +/- 2 yr, HIV duration = 8 +/- 1 yr, body mass index = 22.0 +/- 1.0 kg/m(2), on protease inhibitors and nucleoside analog RT inhibitors) and 12 healthy subjects were studied. HIV-1 patients had a total body fat content (assessed by dual-energy X-ray absorptiometry) similar to that of controls (22 +/- 1 vs. 23 +/- 2%; P = 0.56), with a topographic fat redistribution characterized by reduced fat content in the legs (18 +/- 2 vs. 32 +/- 3%; P < 0.01) and increased fat content in the trunk (25 +/- 2 vs. 19 +/- 2%; P = 0.03). In HIV-positive patients, insulin sensitivity (assessed by QUICKI) was markedly impaired (0.341 +/- 0.011 vs. 0.376 +/- 0.007; P = 0.012). HIV-positive patients also had increased total plasma cholesterol (216 +/- 20 vs. 174 +/- 9 mg/dl; P = 0.05) and triglyceride (298 +/- 96 vs. 87 +/- 11 mg/dl; P = 0.03) concentrations. Muscular triglyceride content assessed by means of (1)H NMR spectroscopy was higher in HIV patients in soleus [92 +/- 12 vs. 42 +/- 5 arbitrary units (AU); P < 0.01] and tibialis anterior (26 +/- 6 vs. 11 +/- 3 AU; P = 0.04) muscles; in a stepwise regression analysis, it was strongly associated with QUICKI (R(2) = 0.27; P < 0.0093). Even if the basal metabolic rate (assessed by indirect calorimetry) was comparable to that of normal subjects, postabsorptive lipid oxidation was significantly impaired (0.30 +/- 0.07 vs. 0.88 +/- 0.09 mg x kg(-1) x min(-1); P < 0.01). In conclusion, lipodystrophy in HIV-1 patients in antiretroviral treatment is associated with intramuscular fat accumulation, which may mediate the development of the insulin resistance syndrome.
对人类免疫缺陷病毒（HIV）阳性患者进行抗逆转录病毒治疗可引发一种脂肪代谢障碍综合征，其特征为外周脂肪减少和中心性肥胖、血脂异常以及胰岛素抵抗。为了检测在该综合征中胰岛素抵抗是否与肌肉对脂肪酸的异常处理有关，对12名HIV-1患者（8名女性/4名男性，年龄 = 26±2岁，HIV感染时间 = 8±1年，体重指数 = 22.0±1.0kg/m²，正在接受蛋白酶抑制剂和核苷类似物逆转录酶抑制剂治疗）和12名健康受试者进行了研究。HIV-1患者的全身脂肪含量（通过双能X线吸收法评估）与对照组相似（22±1%对23±2%；P = 0.56），其脂肪分布特征为腿部脂肪含量降低（18±2%对32±3%；P < 0.01），躯干脂肪含量增加（25±2%对19±2%；P = 0.03）。在HIV阳性患者中，胰岛素敏感性（通过QUICKI评估）明显受损（0.341±0.011对0.376±0.007；P = 0.012）。HIV阳性患者的总血浆胆固醇（216±20对174±9mg/dl；P = 0.05）和甘油三酯（298±96对87±11mg/dl；P = 0.03）浓度也有所升高。通过¹H NMR光谱法评估的肌肉甘油三酯含量在HIV患者的比目鱼肌[92±12对42±5任意单位（AU）；P < 0.01]和胫前肌（26±6对11±3AU；P = 0.04）中更高；在逐步回归分析中，它与QUICKI密切相关（R² = 0.27；P < 0.0093）。即使基础代谢率（通过间接量热法评估）与正常受试者相当，但餐后脂质氧化明显受损（0.30±0.07对0.88±0.09mg·kg⁻¹·min⁻¹；P < 0.01）。总之，接受抗逆转录病毒治疗的HIV-1患者的脂肪代谢障碍与肌肉内脂肪堆积有关，这可能介导了胰岛素抵抗综合征的发生。
