TY - JOUR TI - TIGAR deficiency enhances skeletal muscle thermogenesis by increasing neuromuscular junction cholinergic signaling AU - Tang, Yan AU - Zong, Haihong AU - Kwon, Hyokjoon AU - Qiu, Yunping AU - Pessin, Jacob B AU - Wu, Licheng AU - Buddo, Katherine A AU - Boykov, Ilya AU - Schmidt, Cameron A AU - Lin, Chien-Te AU - Neufer, P Darrell AU - Schwartz, Gary J AU - Kurland, Irwin J AU - Pessin, Jeffrey E A2 - Elmquist, Joel K A2 - Wong, Ma-Li A2 - Saltiel, Alan VL - 11 PY - 2022 DA - 2022/03/07 SP - e73360 C1 - eLife 2022;11:e73360 DO - 10.7554/eLife.73360 UR - https://doi.org/10.7554/eLife.73360 AB - 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. KW - TIGAR KW - cholinergic neurons KW - acetylcholine KW - neuromuscular junction KW - skeletal muscle thermogenesis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -