@article{dc53d49deb1f48a6b4dfdfd205b77e81,
title = "TIGAR deficiency enhances skeletal muscle thermogenesis by increasing neuromuscular junction cholinergic signaling",
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.",
author = "Yan Tang and Haihong Zong and Hyokjoon Kwon and Yunping Qiu and Pessin, {Jacob B.} and Licheng Wu and Buddo, {Katherine A.} and Ilya Boykov and Schmidt, {Cameron A.} and Lin, {Chien Te} and Neufer, {P. Darrell} and Schwartz, {Gary J.} and Kurland, {Irwin J.} and Pessin, {Jeffrey E.}",
note = "Funding Information: We thank Dr. Yu Zhang at the Flow cytometry Core Facility (Albert Einstein College of Medicine) for SH-SY5Y cells FACS sorting. We thank Dr. Xue-liang Du at the Stable Isotope & Metabolomics Core Facility for Seahorse analyses. We also thank Dr. Victor Schuster (Albert Einstein College of Medicine) for the gift of UCP1 knockout mice. We thank Ms. Nicole Fernandez (Ph.D. candidate at the Albert Einstein College of Medicine) for her contribution to the production of Graphic Abstract. This study was supported by grants DK033823 and DK020541 from the National Institutes of Health, and an S10 SIG Award for the Sciex 6500 + QTRAP (1S10OD021798). Funding Information: This study was supported by grants DK033823 and DK020541 from the National Institutes of Health, and an S10 SIG Award for the Sciex 6500 + QTRAP (1S10OD021798). Funder Grant reference number Author National Institutes of Health National Institutes of Health S10 SIG Award for the Sciex 6500+QTRAP DK033823 DK020541 1S10OD021798 Jeffrey Pessin Jeffrey Pessin Irwin J Kurland The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} Tang et al.",
year = "2022",
month = mar,
doi = "10.7554/eLife.73360",
language = "English (US)",
volume = "11",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}