Invalidation of PiT2 in mice leads to an increase in energy expenditure through a UCP1-independent thermogenesis mechanism
M. Guicheteaua (Mlle), M. Guicheteau*a (Mlle), S. Moriceaub (Dr), G. Frangia (Dr), S. Souricea (Mme), X. Prieurc (Dr), L. Becka (Dr), S. Beck-Cormiera (Dr)
a Inserm UMR1229, Nantes, FRANCE ; b Institut Imagine, Paris, FRANCE ; c Inserm UMR1087, Nantes, FRANCE
Objectives. Recently, we have shown that invalidation of the Slc20a2/PiT2 gene in mice (PiT2KO) is determinant for bone quality and strength (Beck-Cormier et al. JBMR 2019). At the time of skeletal analysis, we observed that bone marrow adiposity was altered. This has prompted us to address the role of PiT2 in adipose tissues and energy metabolism.
Material and methods. Fat mass was analysed in 6-month-old male mice during ageing and in a High-Fat Diet (HFD)-induced obesity model. Food intake, oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER) and energy expenditure (EE) were measured in WT (n=19) and PiT2KO (n=15). Histomorphology and gene (Real-time qPCR) and protein (western blot) expression analyses were performed in white and brown adipose tissues (WAT and BAT).
Results. We show that PiT2KO has decreased fat mass with an inhibition of age- and HFD-induced fat gain (p=0.0004 and p=0.008), associated with an inhibition of hepatic steatosis (p=0.0007). Metabolic parameters analyses showed an increase in food intake (p=0.02), VO2 (p=0.008), VCO2 (p=0.03) and EE (p=0.008) and a decrease in RER (p=0.03), indicating a utilization of lipids as a primary fuel source. Surprisingly, the augmentation of EE was not associated with beiging of WAT. Unexpectedly, BAT analyses showed a decrease in UCP1 protein level (p=0.03), suggesting the involvement of UCP1-independent mechanism in the observed phenotype.
Discussion. We identified PiT2 as a new player in energy metabolism and revealed that PiT2KO mice constitutes a new model to better understand pathophysiological mechanisms in obesity.
L’auteur n’a pas transmis de déclaration de conflit d’intérêt.