Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
Am J Clin Nutr. 2011 Dec;94(6):1533-44. doi: 10.3945/ajcn.111.012260. Epub 2011 Nov 9.
Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.
We sought to investigate the effect of acutely elevating leptin to concentrations observed in obese individuals on muscle and adipose tissue metabolism and muscle signaling in healthy lean males.
Healthy, lean, postabsorptive males were infused with either recombinant human leptin (rhleptin; n = 8) or saline (control; n = 8) for 4 h, which elicited leptin concentrations of ~ 20 and ~ 1 ng/mL, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism in vivo were assessed before, during, and 2 h after cessation of the infusion. Skeletal muscle biopsy specimens were obtained to quantify changes in signal transducers and activators of transcription-5'AMP-activated protein kinase (STAT-AMPK) signaling.
During the infusion of rhleptin, no differences in either systemic, skeletal muscle, or adipose tissue glucose or fat metabolism were observed. These observations were made despite increased activation of STAT (~ 17-fold) and AMPK (1.43-fold) after 1 h of rhleptin infusion. After the rhleptin infusion, an increase in systemic palmitate and fat oxidation was observed (P < 0.0003), which likely was caused by a concomitant increase in skeletal muscle palmitate oxidation (P < 0.02). This was observed despite lowered leptin concentrations and basal skeletal muscle STAT-AMPK signaling.
Elevating circulating leptin concentrations to concentrations comparable with those of obese individuals increases human in vivo skeletal muscle signaling through the AMPK pathway and causes an increase in skeletal muscle fatty acid oxidation. Abdominal adipose tissue was unaffected by the acute physiologic increase in leptin concentrations.
与肥胖啮齿动物观察到的显著体重减轻相比，接受瘦素治疗的肥胖和瘦人并未经历令人信服的体重减轻效果。
我们旨在研究急性升高瘦素至肥胖个体中观察到的浓度对健康瘦男性的肌肉和脂肪组织代谢以及肌肉信号的影响。
健康、瘦、吸收后男性接受重组人瘦素（rhleptin；n = 8）或生理盐水（对照；n = 8）输注 4 小时，分别引起瘦素浓度约为 20 和 1 ng/mL。在输注开始前、输注期间和输注停止后 2 小时评估体内系统、骨骼肌和脂肪组织的脂肪和葡萄糖代谢。采集骨骼肌活检标本以定量测定转录激活物 5'-AMP 激活的蛋白激酶（STAT-AMPK）信号转导的变化。
在 rhleptin 输注期间，未观察到系统、骨骼肌或脂肪组织葡萄糖或脂肪代谢的差异。尽管 rhleptin 输注 1 小时后 STAT（~17 倍）和 AMPK（1.43 倍）的激活增加，但仍观察到这些观察结果。rhleptin 输注后，观察到全身棕榈酸和脂肪氧化增加（P < 0.0003），这很可能是由于骨骼肌棕榈酸氧化同时增加（P < 0.02）所致。尽管瘦素浓度降低和基础骨骼肌 STAT-AMPK 信号降低，但仍观察到这种情况。
将循环瘦素浓度升高至与肥胖个体相当的浓度可通过 AMPK 途径增加人体体内骨骼肌信号，并导致骨骼肌脂肪酸氧化增加。急性生理增加瘦素浓度对腹部脂肪组织没有影响。
