Departments of Medicine, Albert Einstein College of Medicine, Bronx, United States.
East Carolina Diabetes and Obesity Institute and the Department of Physiology, Brody School of Medicine East Carolina University, Greenville, United States.
Elife. 2022 Mar 7;11:e73360. doi: 10.7554/eLife.73360.
Cholinergic and sympathetic counter-regulatory networks control numerous physiological functions, including learning/memory/cognition, stress responsiveness, blood pressure, heart rate, and energy balance. As neurons primarily utilize glucose as their primary metabolic energy source, we generated mice with increased glycolysis in cholinergic neurons by specific deletion of the fructose-2,6-phosphatase protein TIGAR. Steady-state and stable isotope flux analyses demonstrated increased rates of glycolysis, acetyl-CoA production, acetylcholine levels, and density of neuromuscular synaptic junction clusters with enhanced acetylcholine release. The increase in cholinergic signaling reduced blood pressure and heart rate with a remarkable resistance to cold-induced hypothermia. These data directly demonstrate that increased cholinergic signaling through the modulation of glycolysis has several metabolic benefits particularly to increase energy expenditure and heat production upon cold exposure.
胆碱能和交感神经的代偿性调节网络控制着许多生理功能，包括学习/记忆/认知、应激反应、血压、心率和能量平衡。由于神经元主要将葡萄糖作为其主要代谢能量来源，我们通过特异性敲除果糖-2,6-磷酸酶蛋白 TIGAR 来增加胆碱能神经元中的糖酵解。稳态和稳定同位素通量分析显示，糖酵解、乙酰辅酶 A 生成、乙酰胆碱水平以及增强乙酰胆碱释放的神经肌肉突触连接簇的密度增加。胆碱能信号的增加降低了血压和心率，对冷诱导的体温过低有明显的抵抗力。这些数据直接证明，通过调节糖酵解增加胆碱能信号传递具有多种代谢益处，特别是在寒冷暴露时增加能量消耗和产热。
