Andersen Ove, Pedersen Steen B, Svenstrup Birgit, Hansen Birgitte R, Paulsen Søren K, Rathje Gulla S, Richelsen Bjørn, Nielsen Jens Ole, Madsbad Sten, Iversen Johan, Haugaard Steen B
Department of Infectious Diseases, Hvidovre University Hospital, DK 2650 Hvidovre, Denmark.
Clin Endocrinol (Oxf). 2007 Aug;67(2):250-8. doi: 10.1111/j.1365-2265.2007.02872.x. Epub 2007 May 24.
Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose tissue in humans possibly through binding to oestrogen-receptor-alpha, which in turn activates anti-lipolytic alpha2A-adrenergic-receptor.
To address these issues circulating pituitary-gonadal-axis hormones and gene expression of receptors in subcutaneous adipose tissue were determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available.
Total and free oestradiol and testosterone were decreased in lipodystrophic patients compared to nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating hormone and prolactin were similar and normal in both study groups. Ratio of subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity, which were all decreased in lipodystrophic patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha.
The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol on the subcutaneous fat depot and lipolysis may be mediated in part through binding to the oestrogen-receptor-alpha, in turn activating anti-lipolytic alpha2A-adrenergic-receptor.
已证明在接受高效抗逆转录病毒疗法（HAART）的人类免疫缺陷病毒（HIV）感染患者中，循环雌二醇和睾酮水平会升高，它们可能会影响脂肪分布和胰岛素敏感性。雌二醇可能通过与雌激素受体α结合来增加人体皮下脂肪组织，而雌激素受体α反过来又会激活抗脂解α2A - 肾上腺素能受体。
为解决这些问题，对31名接受HAART的非糖尿病HIV感染男性患者（其中16名患有脂肪代谢障碍）的循环垂体 - 性腺轴激素以及皮下脂肪组织中受体的基因表达进行了测定，这些患者可进行脂肪分布测量（CT和双能X线吸收法扫描）和胰岛素敏感性测量（高胰岛素正常血糖钳夹试验）。
与无脂肪代谢障碍的患者相比，脂肪代谢障碍患者的总雌二醇、游离雌二醇和睾酮水平降低，而两个研究组的促黄体生成素、促卵泡激素和催乳素水平相似且正常。脂肪代谢障碍患者的皮下与腹部总脂肪量之比、肢体脂肪量和胰岛素敏感性均降低，它们与血浆雌二醇和睾酮均呈正相关（n = 31）。钳夹期间的甘油浓度（脂解标志物）分别与α2A - 肾上腺素能受体的表达、皮下与腹部总脂肪量之比以及肢体脂肪量呈负相关。α2A - 肾上腺素能受体的表达与雌激素受体α的表达呈正相关。
这些结果符合性激素在HIV脂肪代谢障碍男性患者脂肪分布改变和胰岛素敏感性变化中起作用这一假说。雌二醇对皮下脂肪储存和脂解的作用可能部分是通过与雌激素受体α结合来介导的，进而激活抗脂解α2A - 肾上腺素能受体。
