Korbonits M, Trainer P J, Little J A, Edwards R, Kopelman P G, Besser G M, Svec F, Grossman A B
Department of Endocrinology, St. Bartholomew's Hospital, London, UK.
Clin Endocrinol (Oxf). 1997 Jun;46(6):751-7. doi: 10.1046/j.1365-2265.1997.1820979.x.
Leptin is a peptide secreted by white adipose tissue which has been shown to have a major influence on body weight regulation, while animal studies have revealed widespread interconnections between leptin and other endocrine systems, especially with insulin. However, its acute regulation has been little studied in the human. We have therefore investigated the effect of a 1000 kcal meal and fasting on the levels of leptin, insulin and cortisol, in both normal and obese subjects.
We have studied the effect of food and fasting on circulating leptin levels in 20 subjects of normal body mass index (BMI range 18-25) and in a group of 12 moderately-severely obese subjects (BMI range 34-61). We also studied the effect of food and fasting in a patient both before and after the successful removal of a pancreatic insulinoma as a model of excess insulin secretion.
Mean leptin levels were significantly higher in the obese than in the lean group (42.7 +/- 3.41 vs 5.35 +/- 1.55 micrograms/l, mean +/- SEM; P < 0.001), and showed a positive correlation with body mass index (r = +0.71; P < 0.001). Frequent (every 20 minutes) sampling for 3 hours after food did not show any acute changes in circulating leptin levels. On the fasting day we observed a small but significant fall in circulating leptin levels in the last 4 hours of a 20-hour fast in our subjects as a group (92 +/- 0.03% of basal, P = 0.03); however, in the lean subjects the fall was greater (86 +/- 0.04% of basal, P = 0.02) than in the obese, where it did not reach statistical significance (96 +/- 0.05% of basal). Pre-meal and peak insulin levels showed a positive correlation with circulating mean leptin levels (r = +0.65; P < 0.001 and r = +0.78; P < 0.001, respectively) in all subjects, while pre-meal and peak serum cortisol levels showed an inverse relation with leptin levels (r = -0.53; P = 0.002 and r = -0.41; P = 0.02, respectively); this effect was independent of BMI in the obese subjects. In the patient with the insulinoma the markedly elevated insulin and leptin levels measured before the operation returned to normal after removal of the tumour, in accord with reports of experimental animal data that long-term insulin excess per se is associated with increased circulating leptin concentrations.
Leptin is a robust indicator of BMI and insulin levels, both basal and stimulated, but does not change acutely following food. Fasting causes a proportionately greater decline in leptin levels in lean subjects than in obese subjects. Circulating leptin is inversely correlated with the activity of the hypothalamo-pituitary-adrenal axis: whether this is a direct influence of leptin on hypothalamo-pituitary-adrenal activity, or whether both are indirect indicators of body fat stores, requires further investigation.
瘦素是一种由白色脂肪组织分泌的肽，已被证明对体重调节有重大影响，而动物研究揭示了瘦素与其他内分泌系统之间广泛的联系，尤其是与胰岛素的联系。然而，其急性调节在人体中研究较少。因此，我们研究了一顿1000千卡的餐食和禁食对正常及肥胖受试者体内瘦素、胰岛素和皮质醇水平的影响。
我们研究了食物和禁食对20名体重指数正常（BMI范围为18 - 25）的受试者以及一组12名中度至重度肥胖受试者（BMI范围为34 - 61）循环瘦素水平的影响。我们还研究了一名胰腺胰岛素瘤成功切除前后的患者，以其作为胰岛素分泌过多的模型，观察食物和禁食对其的影响。
肥胖组的平均瘦素水平显著高于瘦组（42.7±3.41对5.35±1.55微克/升，平均值±标准误；P<0.001），且与体重指数呈正相关（r = +0.71；P<0.001）。进食后每20分钟进行一次、持续3小时的频繁采样未显示循环瘦素水平有任何急性变化。在禁食日，作为一个整体，我们的受试者在20小时禁食的最后4小时循环瘦素水平出现了虽小但显著的下降（为基础值的92±0.03%，P = 0.03）；然而，瘦受试者的下降幅度（为基础值的86±0.04%，P = 0.02）大于肥胖受试者，肥胖受试者的下降未达到统计学意义（为基础值的96±0.05%）。在所有受试者中，餐前和峰值胰岛素水平与循环平均瘦素水平呈正相关（分别为r = +0.65；P<0.001和r = +0.78；P<0.001），而餐前和峰值血清皮质醇水平与瘦素水平呈负相关（分别为r = -0.53；P = 0.002和r = -0.41；P = 0.02）；在肥胖受试者中，这种效应与BMI无关。在患有胰岛素瘤的患者中，手术前测得的明显升高的胰岛素和瘦素水平在肿瘤切除后恢复正常，这与实验动物数据的报道一致，即长期胰岛素过量本身与循环瘦素浓度升高有关。
瘦素是BMI和基础及刺激状态下胰岛素水平的有力指标，但进食后不会急性变化。禁食导致瘦受试者体内瘦素水平下降的比例大于肥胖受试者。循环瘦素与下丘脑 - 垂体 - 肾上腺轴的活性呈负相关：这是瘦素对下丘脑 - 垂体 - 肾上腺活性的直接影响，还是两者都是体脂储存的间接指标，需要进一步研究。
