Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
Brain Res. 2010 Jul 23;1345:146-55. doi: 10.1016/j.brainres.2010.05.042. Epub 2010 May 23.
In addition to suppressing food intake, leptin reduces body adiposity by altering metabolism within peripheral tissues such as adipose tissue and muscle. Recent work indicates that leptin action within the brain is sufficient to promote glucose uptake and increase fat oxidation within skeletal muscle, and that these effects are dependent on the sympathetic nervous system. To identify neuronal circuits through which leptin impacts skeletal muscle metabolism, we used LepRb-GFP reporter mice in combination with muscle-specific injection of an mRFP-expressing pseudorabies virus (PRV), which acts as a transsynaptic retrograde tracer. Consistent with previous observations in the rat, muscle-specific PRV injection lead to labeling within multiple areas of the hypothalamus and brainstem. However, the only areas in which PRV and LepRb colocalization was detected were within the brainstem nucleus of the solitary tract (NTS) and the hypothalamic retrochiasmatic area. Within the NTS 28.5+/-9.4% of PRV-positive neurons contained LepRb-GFP, while in the RCH 37+/-1.7% of PRV neurons also contained LepRb. In summary, these data clearly implicate the NTS and RCH as key sites through which brain leptin impacts skeletal muscle, and as such provide an anatomical framework within which to interpret physiological data indicating that leptin acts in the brain to influence metabolism within skeletal muscle.
除了抑制食物摄入外，瘦素还通过改变外周组织（如脂肪组织和肌肉）的代谢来减少体脂肪。最近的研究表明，瘦素在大脑中的作用足以促进葡萄糖摄取并增加骨骼肌中的脂肪氧化，并且这些作用依赖于交感神经系统。为了确定瘦素影响骨骼肌代谢的神经元回路，我们使用 LepRb-GFP 报告小鼠结合肌肉特异性注射表达 mRFP 的伪狂犬病毒 (PRV)，PRV 作为顺行逆行示踪剂。与大鼠中的先前观察结果一致，肌肉特异性 PRV 注射导致下丘脑和脑干的多个区域标记。然而，仅在脑干孤束核 (NTS) 和下丘脑视交叉后区检测到 PRV 和 LepRb 共定位。在 NTS 中，28.5+/-9.4%的 PRV 阳性神经元含有 LepRb-GFP，而在 RCH 中，37+/-1.7%的 PRV 神经元也含有 LepRb。总之，这些数据清楚地表明 NTS 和 RCH 是大脑瘦素影响骨骼肌的关键部位，为解释表明瘦素在大脑中作用以影响骨骼肌代谢的生理数据提供了一个解剖学框架。
