Ventromedial hypothalamic melanocortin receptor activation: regulation of activity energy expenditure and skeletal muscle thermogenesis
Ventromedial hypothalamic melanocortin receptor activation: regulation of activity energy expenditure and skeletal muscle thermogenesis
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DOI：
10.1113/jp272352
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发表时间：
2016-09-15
影响因子：
5.5
通讯作者：
Novak, Colleen M.
中科院分区：
文献类型：
--
作者：
Gavini, Chaitanya K.;Jones, William C., II;Novak, Colleen M.
下丘脑腹内侧（VMH）和中央黑素皮质素系统通过调节能量摄入和利用，在调节能量平衡中发挥重要作用。最近的证据表明，VMH的激活改变了骨骼肌的代谢。我们发现vmh内黑素皮质素受体的激活会增加能量消耗和身体活动，将燃料利用转换为脂肪，并降低工作效率，从而使多余的卡路里被骨骼肌作为热量消耗掉。我们还发现vmh内黑素皮质素受体的激活增加了交感神经系统向骨骼肌的流出。vmh内黑素皮质素受体的激活也诱导了肌肉中能量消耗介质表达的显著变化。这些结果支持黑素皮质素受体在VMH中调节骨骼肌代谢的作用。下丘脑腹内侧（VMH）和脑黑素皮质素系统在增加能量消耗（EE）和体力活动、降低食欲和调节交感神经系统（SNS）流出方面都起着重要作用。由于最近的证据表明VMH激活调节骨骼肌代谢，我们提出在VMH和骨骼肌之间存在一条轴，由脑黑素皮质素调节，模拟大脑对棕色脂肪组织的控制。使用非特异性激动剂melanotan II （MTII）激活大鼠VMH中的黑素皮质素受体，与对照剂相比，增加了氧气消耗和EE，降低了呼吸交换率。即使在活动水平保持不变的情况下，vmh内MTII也能增强与活动相关的情感表达。MTII治疗增加了腓肠肌在受控活动期间的散热，以及在家庭笼中。与药物处理的大鼠相比，vmh内黑素皮质素受体激活的大鼠骨骼肌去甲肾上腺素周转率更高，表明SNS对肌肉的驱动增加。最后，vmh内MTII诱导了肌肉能量介质的mRNA表达，而蛋白质水平的短期变化主要局限于磷酸化事件。这些结果支持了一种假设，即黑素皮质素肽在VMH中通过增强外周（包括骨骼肌）中表达的情感表达介质的表达来降低活动经济性，从而增加情感表达。这些数据与黑素皮质素在VMH中调节骨骼肌代谢的作用是一致的。
Key points The ventromedial hypothalamus (VMH) and the central melanocortin system both play vital roles in regulating energy balance by modulating energy intake and utilization. Recent evidence suggests that activation of the VMH alters skeletal muscle metabolism. We show that intra-VMH melanocortin receptor activation increases energy expenditure and physical activity, switches fuel utilization to fats, and lowers work efficiency such that excess calories are dissipated by skeletal muscle as heat. We also show that intra-VMH melanocortin receptor activation increases sympathetic nervous system outflow to skeletal muscle. Intra-VMH melanocortin receptor activation also induced significant changes in the expression of mediators of energy expenditure in muscle. These results support the role of melanocortin receptors in the VMH in the modulation of skeletal muscle metabolism.AbstractThe ventromedial hypothalamus (VMH) and the brain melanocortin system both play vital roles in increasing energy expenditure (EE) and physical activity, decreasing appetite and modulating sympathetic nervous system (SNS) outflow. Because of recent evidence showing that VMH activation modulates skeletal muscle metabolism, we propose the existence of an axis between the VMH and skeletal muscle, modulated by brain melanocortins, modelled on the brain control of brown adipose tissue. Activation of melanocortin receptors in the VMH of rats using a non-specific agonist melanotan II (MTII), compared to vehicle, increased oxygen consumption and EE and decreased the respiratory exchange ratio. Intra-VMH MTII enhanced activity-related EE even when activity levels were held constant. MTII treatment increased gastrocnemius muscle heat dissipation during controlled activity, as well as in the home cage. Compared to vehicle-treated rats, rats with intra-VMH melanocortin receptor activation had higher skeletal muscle norepinephrine turnover, indicating an increased SNS drive to muscle. Lastly, intra-VMH MTII induced mRNA expression of muscle energetic mediators, whereas short-term changes at the protein level were primarily limited to phosphorylation events. These results support the hypothesis that melanocortin peptides act in the VMH to increase EE by lowering the economy of activity via the enhanced expression of mediators of EE in the periphery including skeletal muscle. The data are consistent with the role of melanocortins in the VMH in the modulation of skeletal muscle metabolism.