Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations.
Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations.
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高瘦素血症：青少年肥胖的早期症状。
DOI：
10.1152/ajpendo.1996.271.3.e626
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Sherwin,RS
中科院分区：
文献类型：
--
作者：
Caprio,S;Tamborlane,WV;Silver,D;Robinson,C;Leibel,R;McCarthy,S;Grozman,A;Belous,A;Maggs,D;Sherwin,RS
瘦素是 OB 基因产物，是一种脂肪细胞衍生的循环蛋白。在几种肥胖啮齿动物模型中，例如 db/db 小鼠、fa/fa 大鼠和腹内侧下丘脑损伤小鼠以及成年肥胖受试者，瘦素 mRNA 表达和循环水平升高，表明对其作用有抵抗力。然而，尚不清楚瘦素浓度的升高是否发生在人类肥胖自然进化的早期，或者是对肥胖状态的慢性适应。此外，尚未评估身体脂肪的分布（即内脏脂肪与皮下腹部脂肪）是否影响循环瘦素水平。我们在一组肥胖和非肥胖儿童和年轻人中确定了瘦素水平是否 1) 在肥胖发展早期增加，2) 与磁共振成像测量的特定脂肪库有关，3) 在高胰岛素、正常血糖和高血糖钳夹研究中是否有所不同，以及 4) 男性与女性之间是否有所不同。在基础状态下，肥胖儿童的瘦素水平升高。儿童和成人的瘦素浓度与皮下脂肪库之间存在很强的正相关性（r = 0.84，P < 0.001）。令人惊讶的是，与内脏脂肪量的相关性较弱（r = 0.59，P = 0.001）。在肥胖和非肥胖受试者中，在正常血糖和高血糖高胰岛素条件下，瘦素水平保持不变。还观察到性别对瘦素水平的显着影响。我们的结论是，在青少年肥胖发展的早期，瘦素浓度升高，并且与皮下脂肪量的关系比与内脏脂肪量的关系更密切。胰岛素浓度的急剧增加不会影响循环瘦素水平。
Leptin, the OB gene product, is an adipocyte-derived circulating protein. In several rodent models of obesity, such as the db/db mice, fa/fa rats, and ventromedial hypothalamus-lesioned mice, as well as adult obese subjects, leptin mRNA expression and the circulating levels are elevated, suggesting resistance to its action. However, it is unknown whether the rise in leptin concentration occurs early in the natural evolution of human obesity or is a chronic adaptation to the obese state. Moreover, whether the distribution of body fat (i.e., visceral vs. subcutaneous abdominal fat) influences circulating leptin levels has not been assessed. We have determined in a group of obese and nonobese children and young adults whether leptin levels 1) are increased early in the development of obesity, 2) are related to a specific fat depot measured by magnetic resonance imaging, 3) vary during hyperinsulinemic, euglycemic, and hyperglycemic clamp studies, and 4) are different in males vs. females. In the basal state, leptin levels were elevated in obese children. Children and adults demonstrated a strong positive correlation between leptin concentrations and the subcutaneous fat depot (r = 0.84, P < 0.001). Surprisingly, a weaker correlation was found with visceral fat mass (r = 0.59, P = 0.001). Leptin levels remained unchanged under both euglycemic and hyperglycemic hyperinsulinemic conditions in both obese and nonobese subjects. A pronounced effect of gender on leptin levels was also observed. We conclude that, early in the development of juvenile obesity, leptin concentrations are elevated and are more closely linked to subcutaneous than visceral fat mass. Acute increases in insulin concentrations do not affect circulating leptin levels.