Extra-adipocyte leptin release in human obesity and its relation to sympathoadrenal function

Extra-adipocyte leptin release in human obesity and its relation to sympathoadrenal function
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DOI:
10.1152/ajpendo.00489.2003
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发表时间:
2004-05-01
影响因子:
5.1
通讯作者:
Esler, M
Esler, M
中科院分区:
医学2区
文献类型:
--
作者:
Eikelis, N;Lambert, G;Esler, M

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人类交感肾上腺髓质系统与脂肪细胞激素瘦素之间的联系存在争议。我们测量了 22 名接受动脉和中心静脉导管插入术的瘦[体重指数 (BMI) 28) 血压正常男性的去甲肾上腺素总溢出量和局部去甲肾上腺素溢出量、肾上腺素分泌率和脂肪细胞外瘦素释放。由于瘦素的血浆清除主要是通过肾脏清除,因此对于处于稳态的男性,我们可以估计从肾血浆瘦素提取中释放到血浆的全身瘦素。肥胖男性全身瘦素释放量为 1,950 +/- 643(平均值 +/- SE)纳克/分钟,瘦男性为 382 +/- 124 纳克/分钟(P < 0.05)。总去甲肾上腺素溢出率和肾去甲肾上腺素溢出率与全身瘦素分泌率直接相关。瘦素从多个非脂肪细胞部位释放,我们通过同时动静脉采血进行测试。我们发现大脑瘦素释放对血浆瘦素库的贡献惊人地大,为 529 +/- 175 ng/min(> 40% 全身瘦素释放),肥胖男性的瘦素释放量高于瘦男性,分别为 935 +/- 321 与 160 +/- 59 ng/min (P = 0.045)。在测量瘦素的同时,我们还量化了大脑血清素周转率和神经肽 Y (NPY) 的颈静脉溢出。肥胖男性的大脑血清素周转率高于瘦男性,分别为 227 +/- 112 纳克/分钟 vs. 21±14 纳克/分钟 (P = 0.019),大脑中 NPY 的溢出量也高于瘦男性,分别为 12.9 +/- 1.4 纳克/分钟 vs. 5.3 +/- 2.2 纳克/分钟 (P = 0.042)。这些结果表明,瘦素在大脑内释放,并且在肥胖人群中以更高的速度释放,其中也存在大脑血清素能和 NPY 机制的激活。
The link between the human sympathoadrenalmedullary system and the adipocyte hormone leptin is controversial. We measured total and regional norepinephrine spillover, epinephrine secretion rate, and extra-adipocyte leptin release in 22 lean [body mass index (BMI) 28) normotensive men who underwent arterial and central venous catheterization. Because plasma clearance of leptin is primarily by renal removal, for men at steady state we could estimate whole body leptin release to plasma from renal plasma leptin extraction. Whole body leptin release was 1,950 +/- 643 (means +/- SE) ng/min in obese men and 382 +/- 124 ng/min in lean men (P < 0.05). Total and renal norepinephrine spillover rates correlated directly with whole body leptin secretion rate. Leptin is released from multiple nonadipocyte sites, which we tested by use of simultaneous arteriovenous blood sampling. We found a surprisingly large contribution of brain leptin release to the plasma leptin pool, 529 +/- 175 ng/min (>40% whole body leptin release), with greater leptin release in obese than in lean men, 935 +/- 321 vs. 160 +/- 59 ng/min (P = 0.045). In parallel with leptin measurements, we also quantified brain serotonin turnover and jugular overflow of neuropeptide Y (NPY). Brain serotonin turnover was higher in obese than in lean men, 227 +/- 112 vs. 21 14 ng/min (P = 0.019), as was overflow of NPY from the brain, 12.9 +/- 1.4 vs. 5.3 +/- 2.2 ng/min (P = 0.042). These results suggest that leptin is released within the brain and at an increased rate in obese humans, in whom activation of brain serotonergic and NPY mechanisms also exists.