Tang 2022 Elife

Tang Y, Zong H, Kwon H, Qiu Y, Pessin JB, Wu L, Buddo KA, Boykov I, Schmidt CA, Lin CT, Neufer PD, Schwartz GJ, Kurland IJ, Pessin JE (2022) TIGAR deficiency enhances skeletal muscle thermogenesis by increasing neuromuscular junction cholinergic signaling. https://doi.org/10.7554/elife.73360

» Elife 11:e73360. PMID: 35254259 Open Access

Tang Yan, Zong Haihong, Kwon Hyokjoon, Qiu Yunping, Pessin Jacob B, Wu Licheng, Buddo Katherine A, Boykov Ilya, Schmidt Cameron A, Lin Chien-Te, Neufer P Darrell, Schwartz Gary J, Kurland Irwin J, Pessin Jeffrey E (2022) Elife

Abstract: 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. • Keywords: TIGAR, Acetylcholine, Cell biology, Cholinergic neurons, Mouse, Neuromuscular junction, Neuroscience, Skeletal muscle thermogenesis • Bioblast editor: Plangger M • O2k-Network Lab: US NC Greenville Neufer PD

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: OXPHOS 

HRR: Oxygraph-2k 

2023-08