TY - JOUR
T1 - Stimulation of P2X7 Enhances Whole Body Energy Metabolism in Mice
AU - Giacovazzo, Giacomo
AU - Fabbrizio, Paola
AU - Apolloni, Savina
AU - Coccurello, Roberto
AU - Volonté, Cinzia
PY - 2019/8/21
Y1 - 2019/8/21
N2 - The P2X7 receptor, a member of the ionotropic purinergic P2X family of extracellular ATP-gated receptors, exerts strong trophic effects when tonically activated in cells, in addition to cytotoxic effects after a sustained activation. Because of its widespread distribution, P2X7 regulates several cell- and tissue-specific physiological functions, and is involved in a number of disease conditions. A novel role has recently emerged for P2X7 in the regulation of glucose and energy metabolism. In previous work, we have demonstrated that genetic depletion, and to a lesser extent also pharmacological inhibition of P2X7, elicits a significant decrease of the whole body energy expenditure and an increase of the respiratory exchange ratio. In the present work, we have investigated the effects of P2X7 stimulation in vivo on the whole body energy metabolism. Adult mice were daily injected with the specific P2X7 agonist 2′(3′)-O-(4-Benzoylbenzoyl)adenosine 5′-triphosphate for 1 week and subjected to indirect calorimetric analysis for 48 h. We report that 2′(3′)-O-(4-Benzoylbenzoyl)adenosine 5′-triphosphate increases metabolic rate and O2 consumption, concomitantly decreasing respiratory rate and upregulating NADPH oxidase 2 in gastrocnemius and tibialis anterior muscles. Our results indicate a major impact on energy homeostasis and muscle metabolism by activation of P2X7.
AB - The P2X7 receptor, a member of the ionotropic purinergic P2X family of extracellular ATP-gated receptors, exerts strong trophic effects when tonically activated in cells, in addition to cytotoxic effects after a sustained activation. Because of its widespread distribution, P2X7 regulates several cell- and tissue-specific physiological functions, and is involved in a number of disease conditions. A novel role has recently emerged for P2X7 in the regulation of glucose and energy metabolism. In previous work, we have demonstrated that genetic depletion, and to a lesser extent also pharmacological inhibition of P2X7, elicits a significant decrease of the whole body energy expenditure and an increase of the respiratory exchange ratio. In the present work, we have investigated the effects of P2X7 stimulation in vivo on the whole body energy metabolism. Adult mice were daily injected with the specific P2X7 agonist 2′(3′)-O-(4-Benzoylbenzoyl)adenosine 5′-triphosphate for 1 week and subjected to indirect calorimetric analysis for 48 h. We report that 2′(3′)-O-(4-Benzoylbenzoyl)adenosine 5′-triphosphate increases metabolic rate and O2 consumption, concomitantly decreasing respiratory rate and upregulating NADPH oxidase 2 in gastrocnemius and tibialis anterior muscles. Our results indicate a major impact on energy homeostasis and muscle metabolism by activation of P2X7.
KW - BzATP
KW - energy expenditure
KW - fatty acid oxidation
KW - oxygen consumption
KW - P2X7 receptor
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U2 - 10.3389/fncel.2019.00390
DO - 10.3389/fncel.2019.00390
M3 - Article
AN - SCOPUS:85072740534
VL - 13
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
M1 - 390
ER -