Selective parasympathetic innervation of subcutaneous and intra-abdominal fat - functional implications
Selective parasympathetic innervation of subcutaneous and intra-abdominal fat - functional implications
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DOI：
10.1172/jci200215736
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发表时间：
2002-11-01
影响因子：
15.9
通讯作者：
Buijs, RM
中科院分区：
文献类型：
--
作者：
Kreier, F;Fliers, E;Buijs, RM
丰富的临床流行病学数据腹腔内脂肪堆积和发病率之间的关联形成鲜明对比，缺乏知识的脂肪分布的决定因素，这不能仅仅解释在体液因素。如果涉及到神经元的控制，到目前为止，据报道脂肪组织只受交感神经系统的支配，以其分解代谢作用而闻名。我们假设在脂肪组织中存在副交感神经输入刺激合成代谢过程。大鼠腹腔内脂肪垫首先交感神经切断，然后注射逆行跨神经示踪剂伪狂犬病病毒（PRV）。由此产生的标记PRV的迷走神经运动核的脑干表明，脂肪组织接受迷走神经输入。接下来，我们通过将脂肪垫特异性迷走神经切断术与高胰岛素正葡萄糖钳夹和RT-PCR分析相结合来评估这些发现的生理影响。胰岛素介导的葡萄糖和FFA摄取分别减少了33%和36%，而分解代谢酶对葡萄糖敏感的脂肪酶的活性增加了51%。此外，Leptin和Leptin mRNA的表达下降，而脂联素mRNA没有变化。所有这些数据表明迷走神经输入脂肪组织的合成代谢作用。最后，我们证明了自主神经系统的中央部分内的躯体，因为腹内和皮下脂肪垫似乎是由单独的交感神经和副交感神经运动神经元支配。总之，对脂肪组织的副交感神经输入以合成代谢的方式清楚地调节其胰岛素敏感性和葡萄糖和FFA代谢。这些研究结果的影响（病理）生理学的脂肪分布进行了讨论。
The wealth of clinical epidemiological data on the association between intra-abdominal fat accumulation and morbidity sharply contrasts with the paucity of knowledge about the determinants of fat distribution, which cannot be explained merely in terms of humoral factors. If it comes to neuronal control, until now, adipose tissue was reported to be innervated by the sympathetic nervous system only, known for its catabolic effect. We hypothesized the presence of a parasympathetic input stimulating anabolic processes in adipose tissue. Intra-abdominal fat pads in rats were first sympathetically denervated and then injected with the retrograde transneuronal tracer pseudorabies virus (PRV). The resulting labeling of PRV in the vagal motor nuclei of the brain stem reveals that adipose tissue receives vagal input. Next, we assessed the physiological impact of these findings by combining a fat pad-specific vagotomy with a hyperinsulinemic euglycemic clamp and RT-PCR analysis. Insulin-mediated glucose and FFA uptake were reduced by 33% and 36%, respectively, whereas the activity of the catabolic enzyme hormone-sensitive lipase increased by 51%. Moreover, expression of resistin and leptin mRNA decreased, whereas adiponectin mRNA did not change. All these data indicate an anabolic role for the vagal input to adipose tissue. Finally, we demonstrate somatotopy within the central part of the autonomic nervous system, as intra-abdominal and subcutaneous fat pads appeared to be innervated by separate sympathetic and parasympathetic motor neurons. In conclusion, parasympathetic input to adipose tissue clearly modulates its insulin sensitivity and glucose and FFA metabolism in an anabolic way. The implications of these findings for the (patho)physiology of fat distribution are discussed.