Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the lateral hypothalamus.
Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the lateral hypothalamus.
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作者：
Morgan DA;McDaniel LN;Yin T;Khan M;Jiang J;Acevedo MR;Walsh SA;Ponto LL;Norris AW;Lutter M;Rahmouni K;Cui H
黑皮质素 4 受体 (MC4R) 信号传导介导多种生理功能，包括能量平衡、葡萄糖稳态和自主活动。尽管已知下丘脑外侧区 (LHA) 表达 MC4R 并接收来自瘦素反应性弓状原阿黑皮素神经元的输入，但 LHA 中 MC4R 的生理功能尚不完全清楚。我们报告 MC4RLHA 信号传导调节葡萄糖耐量和交感神经活动。恢复 LHA 中 MC4R 的表达可改善肥胖 MC4R 缺失小鼠的葡萄糖耐受不良，而不影响体重或循环胰岛素水平。氟脱氧葡萄糖介导的全身葡萄糖摄取追踪将肩胛间棕色脂肪组织 (iBAT) 确定为 MC4RLHA 小鼠葡萄糖摄取增加的主要来源。直接多纤维交感神经记录进一步表明，MC4RLHA 小鼠中 iBAT 的交感神经流量显着增加，这伴随着 iBAT 中 Glut4 表达的显着升高。最后，双侧 iBAT 去神经可阻止 MC4RLHA 信号传导的葡萄糖调节作用。这些结果确定了 MC4RLHA 信号在控制交感神经活动和独立于能量平衡的葡萄糖耐量方面的新作用。
Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4RLHA signaling regulates glucose tolerance and sympathetic nerve activity. Restoring expression of MC4Rs specifically in the LHA improves glucose intolerance in obese MC4R-null mice without affecting body weight or circulating insulin levels. Fluorodeoxyglucose-mediated tracing of whole-body glucose uptake identifies the interscapular brown adipose tissue (iBAT) as a primary source where glucose uptake is increased in MC4RLHA mice. Direct multifiber sympathetic nerve recording further reveals that sympathetic traffic to iBAT is significantly increased in MC4RLHA mice, which accompanies a significant elevation of Glut4 expression in iBAT. Finally, bilateral iBAT denervation prevents the glucoregulatory effect of MC4RLHA signaling. These results identify a novel role for MC4RLHA signaling in the control of sympathetic nerve activity and glucose tolerance independent of energy balance.
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影响因子：
16.2
作者：
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DOI：
10.1152/ajpregu.00174.2008
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10.1152/ajpendo.00488.2012
发表时间：
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