Receptor-mediated regional sympathetic nerve activation by leptin
Receptor-mediated regional sympathetic nerve activation by leptin
复制标题
DOI：
10.1172/jci119532
复制
发表时间：
1997-07-15
影响因子：
15.9
通讯作者：
Sivitz, WI
中科院分区：
文献类型：
--
作者：
Haynes, WG;Morgan, DA;Sivitz, WI
瘦素是由脂肪组织产生的肽类激素，其中枢作用是降低食欲和增加能量消耗。虽然瘦素增加产热组织中的去甲肾上腺素周转，但瘦素对直接测量的产热组织和其他组织的交感神经活性的影响尚不清楚。我们检查了静脉内瘦素和载体对棕色脂肪组织、肾脏、后肢、和肾上腺中。静脉输注小鼠瘦素超过3小时（总剂量10- 1，000 μ g/kg）增加免疫反应性小鼠瘦素的血浆浓度高达50倍。瘦素缓慢增加棕色脂肪组织的交感神经活动（1，000 μ g/kg时为+286+/-64%; P = 0.002）。令人惊讶的是，瘦素输注也使肾交感神经活性逐渐增加（1,000 μ g/kg时为+228+/-63%，P = 0.0008）。瘦素对交感神经活动的影响呈剂量依赖性，其阈值剂量为100 μ g/kg。瘦素也增加交感神经活动的后肢（+287+/-60%）和肾上腺（388+/-171%），尽管总体交感神经活性增加，但瘦素不增加动脉压或心率，瘦素不改变血浆葡萄糖和胰岛素浓度，输注赋形剂不改变交感神经活性，肥胖Zucker大鼠，已知在瘦素受体基因中具有突变的人对瘦素的交感神经兴奋作用具有抗性，尽管获得了更高的血浆瘦素浓度。这些数据表明瘦素增加产热交感神经活性，并揭示了瘦素对总体交感神经运输的意想不到的刺激作用。
Leptin is a peptide hormone produced by adipose tissue which acts centrally to decrease appetite and increase energy expenditure, Although leptin increases norepinephrine turnover in thermogenic tissues, the effects of leptin on directly measured sympathetic nerve activity to thermogenic and other tissues are not known, We examined the effects of intravenous leptin and vehicle on sympathetic nerve activity to brown adipose tissue, kidney, hindlimb, and adrenal gland in anesthetized Sprague-Dawley rats. Intravenous infusion of mouse leptin over 3 h (total dose 10-1,000 mu g/kg) increased plasma concentrations of immunoreactive murine leptin up to 50-fold. Leptin slowly increased sympathetic nerve activity to brown adipose tissue (+286+/-64% at 1,000 mu g/kg; P = 0.002). Surprisingly, leptin infusion also produced gradual increases in renal sympathetic nerve activity (+228+/-63% at 1,000 mu g/kg; P = 0.0008). The effect of leptin on sympathetic nerve activity was dose dependent, with a threshold dose of 100 mu g/kg. Leptin also increased sympathetic nerve activity to the hindlimb (+287+/-60%) and adrenal gland (388+/-171%), Despite the increase in overall sympathetic nerve activity, leptin did not increase arterial pressure or heart rate, Leptin did not change plasma glucose and insulin concentrations, Infusion of vehicle did not alter sympathetic nerve activity, Obese Zucker rats, known to possess a mutation in the gene for the leptin receptor, were resistant to the sympathoexcitatory effects of leptin, despite higher achieved plasma leptin concentrations, These data demonstrate that leptin increases thermogenic sympathetic nerve activity and reveal an unexpected stimulatory effect of leptin on overall sympathetic nerve traffic.