Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia.
Hypertension. 2010 Apr;55(4):862-8. doi: 10.1161/HYPERTENSIONAHA.109.141119. Epub 2010 Mar 1.
The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (P<0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (P<0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (r=0.87; P<0.01). Intracerebroventricular leptin administration (5 to 100 microg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: -54%, paraventricular: -69%, and dorsomedial hypothalamus: -65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.
瘦素作为脂肪细胞因子通过中枢作用激活交感神经系统，被认为是肥胖导致高血压发展的主要机制之一。然而，肥胖时交感神经活性升高的直接证据仅限于肌肉。本研究探讨了高脂肪饮食（HFD）对肾交感神经活性和心血管的影响，以及对侧脑室给予瘦素敏感性的变化。4 周喂养 13.5%HFD 的新西兰白兔体重增加适度，但内脏脂肪堆积增加 2-3 倍。HFD 后 3 周，平均动脉压、心率和血浆去甲肾上腺素浓度分别增加 8%、26%和 87%（P<0.05）。肾交感神经活性在 HFD 组比对照组高 48%（P<0.05），与血浆瘦素呈正相关（r=0.87；P<0.01）。侧脑室给予瘦素（5 至 100 微克）可使两组的平均动脉压相似升高，但 HFD 喂养的兔子肾交感神经活性升高更多。相比之下，在与瘦素的食欲和交感作用有关的重要区域（弓状核：-54%，室旁核：-69%，和背内侧下丘脑：-65%），HFD 组给予侧脑室瘦素后表达 c-Fos 的神经元减少。这些结果表明，通过摄入 HFD 导致内脏脂肪堆积，从而导致明显的交感神经激活，这与对中枢性交感兴奋作用的瘦素反应性增加有关。瘦素对下丘脑神经元激活的这种矛盾性降低表明，这些动物存在明显的“选择性瘦素抵抗”。
