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

Giacomo Giacovazzo, Savina Apolloni, Roberto Coccurello

Research output: Contribution to journalArticlepeer-review

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. Decreased EE and fat oxidation is predictive of body weight gain, which was here confirmed. Taken together, our data provide evidence that P2X7 loss of function produces defective energy homeostasis that, together with disrupted adipogenesis, might help to explain accumulation of adipose tissue and contribute to disclose the potential role of P2X7 in metabolic diseases.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalPurinergic Signalling
DOIs
Publication statusAccepted/In press - May 12 2018

Keywords

  • Energy expenditure
  • Energy metabolism
  • Fat acids oxidation
  • Obesity
  • P2X7 receptor
  • Purinergic signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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