Thesis defense Marie Guicheteau

Le 11 October 2024

14h en amphi 5 de médecine.

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Title of the thesis : Study of the role of PiT2 in energy metabolism

Equipe

Team III - Vascular & Pulmonary Diseases

Directrice de thèse

Co-directeur

Rapporteurs

Cédric MORO, PhD, DR, Université de Toulouse Paul Sabatier, INSERM/UPS UMR1297
Julien PACCOU, PU-PH, CHU Lille/MABLab, ULR4490

Examinateurs

Audrey CARRIERE, CR, Université de Toulouse Paul Sabatier, UMR1301 Inserm, UMR5070 CNRS
Nicolas VENTECLEF, PhD, DR, Université de Paris Cité, INEM

Abstract

The aim of my thesis was to investigate the role of Slc20a2/PiT2 in the regulation of energy metabolism. Analysis of the metabolic phenotype of Slc20a2-/- mice shows that they have a reduction in fat mass volume compared to control mice, which is associated with an increase in energy expenditure, but no change in food intake, physical activity or intestinal absorption of lipids. We show that the increase in energy expenditure is associated with an increase in brown adipose tissue (BAT) activity. The increase in lipolysis in BAT and white adipose tissue (WAT) further suggests that the fatty acids released serve as a substrate for BAT activity. Unexpectedly, increased BAT activity was not associated with increased expression of UCP1 or genesinvolved in alternative UCP1-independent pathways, nor with browning of WAT in Slc20a2-/- mice. In pathology, increased BAT activity may be used to counteract excessive energy intake. We therefore subjected Slc20a2-/- mice to a high-fat diet. Although our initial results showed that Slc20a2-/- mice were resistant to obesity, at the end of my thesis we could not confirm these results. Finally, the invalidation of Slc20a2 specifically in adipocytes suggests that the metabolic phenotype of Slc20a2-/- mice is the consequence of the loss of PiT2 in another organ. This work has identified PiT2 as an important regulator of energy metabolism whose mechanisms of action remain largely unexplored.

Mis à jour le 01 October 2024.