Metabolomic study of TNAP deficiency in mice organs and its implications in lipid metabolism.

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Drevet Mulard, Eva | Gilard, Véronique | Balayssac, Stéphane | Briolay, Anne | Bessueille, Laurence | J. P. Rautureau, Gilles | Magne, David

Edité par CCSD -

International audience. Hypophosphatasia, a rare genetic disorder resulting from Tissue Nonspecific Alkaline Phosphatase (TNAP) deficiency, manifests with a spectrum of symptoms ranging from epileptic crises, bone fractures, and hypotonia in moderate forms (1 in 100,000 individuals) to life-threatening conditions in the most severe cases (1 in 300,000 individuals). While TNAP is an enzyme distributed throughout the body, the intricacies of its action in various organs remain largely unresolved, particularly its potential involvement in energy metobolism. In this study, we employed Nuclear Magnetic Resonance (NMR) spectroscopy to delineate the action of TNAP in crucial mice organs (liver, kidneys, and muscles) as well as serum. All mice (n= 40) underwent a 12-hour fasting period and half were refed while the others remained fasted. Half the mice received an intraperitoneal injection of a TNAP inhibitor. We then determined the metabolomic profiles using NMR (800 MHz) of organs after metabolite extraction, and serum. This experimental design allowed us to generate tables detailing metabolite concentrations in organs under four conditions: with or without refeeding, and with or without TNAP inhibition. Employing a non-targeted approach, our findings unveil new potential TNAP substrates, shedding light on their potential implication in lipid metabolism.

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