The mouse liver displays circadian rhythms in the phospholipid metabolism and in the activity of its synthesizing enzymes

GORNE, LUCAS D.; ACOSTA RODRIGUEZ, VICTORIA A.; PASQUARÉ, S.J.; SALVADOR, G.A.; GIUSTO, N.M.; GUIDO, MARIO E.

Montana

Congreso; 14th Biennial Meeting. Society for Research in Biological Rhythms.; 2014

Society for Research in Biological Rhythms (SRBR)

Disruption of circadian clocks leads to severe metabolic disorders and pathologies involving lipid metabolism such as obesity and diabetes. Glycerophospholipids (GPLs) are the most abundant class of phospholipids that constitutes cell membranes and their synthesis is a crucial process in the liver function; however, its temporal regulation remains unknown. Here we investigated whether the GPL metabolism oscillates in mouse liver fed ad libitum. We first found that the endogenous content of some GPLs (phosphatidylcholine: PC, phosphatidylinositol: PI) exhibited a clear daily rhythmicity in mouse livers collected under constant darkness. Overall, GPLs showed higher levels during the subjective day and lowest levels at CT 20 in the subjective night. In addition, the activity of GPL-synthesizing and -remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1, /Lipin) and lysophospholipid acyltransferases (LPLATs) displayed significant variations with higher levels during the subjective day and dusk. Since PC is an essential and abundant hepatic GPL exhibiting a highly regulated process of synthesis, we evaluated whether the enzymes involved in PC synthesis exhibit a temporal regulation in both expression and activity. In the liver, PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as one of the key regulatory enzymes or through an alternative pathway catalyzed by the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) converting PE into PC. In this respect, we observed that the ratio in the endogenous PC to PE content exhibited daily variations with the lowest levels during the subjective night. In addition, we found significant oscillations in ChoKα and PEMT mRNA expression with maximal levels during the subjective night (CT 16-20). Results demonstrate that the metabolism of liver GPLs from LD-synchronized mice oscillates rhythmically with a precise temporal control in the expression and activities of specific synthesizing/remodeling enzymes. Our findings provide new insights to understand the temporal regulation of biological processes implicating phospholipid metabolism.