Metabolism, Diabetes and Obesity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Sci Adv. 2021 Feb 26;7(9). doi: 10.1126/sciadv.abf4100. Print 2021 Feb.
The importance of hypothalamic insulin signaling on feeding and glucose metabolism remains unclear. We report that insulin acts on AgRP neurons to acutely decrease meal size and thereby limit postprandial glucose and insulin excursions. The promotion of insulin signaling in AgRP neurons decreased meal size without altering total caloric intake, whereas the genetic ablation of the insulin receptor had the opposite effect. The promotion of insulin signaling also decreased the intake of sucrose-sweetened water or high-fat food over standard chow, without influencing food-seeking and hedonic behaviors. The ability of heightened insulin signaling to override the hedonistic consumption of highly palatable high-fat food attenuated the development of systemic insulin resistance, without affecting body weight. Our findings define an unprecedented mechanism by which insulin acutely influences glucose metabolism. Approaches that enhance insulin signaling in AgRP neurons may provide a means for altering feeding behavior in a nutrient-dense environment to combat the metabolic syndrome.
下丘脑胰岛素信号对摄食和葡萄糖代谢的重要性尚不清楚。我们报告称，胰岛素作用于 AgRP 神经元可急性减少进食量，从而限制餐后血糖和胰岛素波动。促进 AgRP 神经元中的胰岛素信号传递可减少进食量而不改变总热量摄入，而胰岛素受体的基因缺失则产生相反的效果。促进胰岛素信号传递还可减少蔗糖甜味水或高脂肪食物的摄入，而不影响食物寻求和享乐行为。增强胰岛素信号传递的能力可以克服对高可口高脂肪食物的享乐性消费，从而减轻全身胰岛素抵抗的发展，而不影响体重。我们的发现定义了一种前所未有的机制，即胰岛素可急性影响葡萄糖代谢。增强 AgRP 神经元中胰岛素信号传递的方法可能为改变营养丰富环境中的摄食行为提供一种手段，以对抗代谢综合征。
