Nielsen Steen, Jørgensen Jens O L, Hartmund Tore, Nørrelund Helene, Nair K S, Christiansen Jens Sandahl, Møller Niels
Medical Department M, Aarhus University Hospital, Aarhus C, Denmark.
Growth Horm IGF Res. 2002 Dec;12(6):425-33. doi: 10.1016/s1096-6374(02)00119-3.
Our study was conducted to define the roles of lowering circulating free fatty acids (FFA) and of growth hormone (GH) replacement on protein metabolism in GH deficient patients. To isolate the specific effects of FFA and GH we studied seven adult subjects with GH deficiency four times: (A) with administration of GH and Acipimox (an inhibitor of lipolysis), (B) with GH, without Acipimox, (C) without GH, with Acipimox and (D) without either. Each study included a 3 h basal period and a 3 h euglycemic clamp. Amino acid metabolism was assessed by stable isotope dilution technique at the whole body level and across the forearm. Overall, we saw no intervention effect on protein metabolism, but when the two situations in which Acipimox was given were combined, Acipimox decreased basal plasma FFA concentrations by 75% and increased serum urea concentrations by 20%, whole body appearance rates (reflecting protein degradation) of phenylalanine (by 7%) and tyrosine (by 11%) and protein synthesis rates for phenylalanine (by 7%), whereas phenylalanine-to-tyrosine conversion was unaffected. Acipimox more than doubled net forearm phenylalanine release during the clamp and increased basal forearm phenylalanine disappearance (reflecting muscle protein synthesis). During the clamp whole body amino acid fluxes and phenylalanine-to-tyrosine conversion decreased together with a decrease in forearm protein breakdown. GH replacement did not affect any of these metabolic parameters. Although we failed to show any role for GH, the results show that lowering of FFA concentrations with Acipimox has pronounced effects on protein metabolism, including increased whole body and forearm protein breakdown, together with increased protein synthesis systemically and locally in the forearm. The increase in serum urea and a doubling of net forearm phenylalanine release after lowering of FFA strongly indicate that the overall effect is catabolic and supports a pivotal protein conserving role of lipids.
我们开展这项研究的目的是确定降低循环游离脂肪酸（FFA）以及生长激素（GH）替代治疗对生长激素缺乏患者蛋白质代谢的作用。为了分离FFA和GH的特定作用，我们对7名成年生长激素缺乏受试者进行了4次研究：（A）给予GH和阿西莫司（一种脂解抑制剂）；（B）给予GH，不给予阿西莫司；（C）不给予GH，给予阿西莫司；（D）两者均不给予。每项研究包括3小时的基础期和3小时的正常血糖钳夹期。通过稳定同位素稀释技术在全身水平和前臂评估氨基酸代谢。总体而言，我们未观察到对蛋白质代谢的干预作用，但当将给予阿西莫司的两种情况合并时，阿西莫司使基础血浆FFA浓度降低了75%，血清尿素浓度升高了20%，苯丙氨酸（升高7%）和酪氨酸（升高11%）的全身出现率（反映蛋白质降解）以及苯丙氨酸的蛋白质合成率（升高7%）均升高，而苯丙氨酸向酪氨酸的转化未受影响。在钳夹期间，阿西莫司使前臂苯丙氨酸净释放增加了一倍多，并增加了基础前臂苯丙氨酸消失率（反映肌肉蛋白质合成）。在钳夹期间，全身氨基酸通量和苯丙氨酸向酪氨酸的转化随着前臂蛋白质分解的减少而降低。GH替代治疗未影响任何这些代谢参数。尽管我们未能证明GH有任何作用，但结果表明，使用阿西莫司降低FFA浓度对蛋白质代谢有显著影响，包括全身和前臂蛋白质分解增加，以及前臂局部和全身蛋白质合成增加。降低FFA后血清尿素升高以及前臂苯丙氨酸净释放增加一倍，强烈表明总体效应是分解代谢的，并支持脂质在蛋白质保存方面的关键作用。
