Loss of P2X7 receptor function dampens whole body energy expenditure and fatty acid oxidation

Purinergic Signalling
Giacomo GiacovazzoRoberto Coccurello

Abstract

The established role of ATP-responsive P2X7 receptor in inflammatory, neurodegenerative, and immune diseases is now expanding to include several aspects of metabolic dysregulation. Indeed, P2X7 receptors are involved in β cell function, insulin secretion, and liability to diabetes, and loss of P2X7 function may increase the risk of hepatic steatosis and disrupt adipogenesis. Recently, body weight gain, abnormal lipid accumulation, adipocyte hyperplasia, increased fat mass, and ectopic fat distribution have been found in P2X7 KO mice. Here, we hypothesized that such clinical picture of dysregulated lipid metabolism might be the result of altered in vivo energy metabolism. By indirect calorimetry, we assessed 24 h of energy expenditure (EE) and respiratory exchange ratio (RER) as quotient of carbohydrate to fat oxidation in P2X7 KO mice. Moreover, we assessed the same parameters in aged-matched WT counterparts that underwent a 7-day treatment with the P2X7 antagonist A804598. We found that loss of P2X7 function elicits a severe decrease of EE that was less pronounced in A804598-treated mice. In parallel, P2X7KO mice show a drastic increase of RER, thus indicating the occurrence of a greater ratio of carbohydrate to fat oxidation....Continue Reading

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Citations

Mar 14, 2020·Cell & Bioscience·Danwen WangZhiling Sun
Sep 10, 2019·Frontiers in Cellular Neuroscience·Giacomo GiacovazzoCinzia Volonté
Aug 8, 2021·Cells·Izadora Lorrany Alves RabeloClaudiana Lameu
Aug 5, 2021·Purinergic Signalling·Serena Janho Dit HreichValérie Vouret-Craviari
Nov 17, 2021·British Journal of Pharmacology·Silvia ScaricamazzaAlberto Ferri

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