The mouse liver displays daily rhythms in the metabolism of phospholipids and in the activity of lipid synthesizing enzymes

Abstract

The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light–dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKα and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes.

• Circadian rhythm
• mouse liver
• peripheral oscillator
• phospholipid metabolism

Acknowledgments

The authors thank Dr Daniela Bussolino for her excellent technical support and collaboration.

Declaration of interest

The authors report no conflicts of interest.

This work was supported by Agencia Nacional de Promoción Científica y Tecnológica (FONCyT) (PICT 2004 N° 967, PICT 2006 N° 898 and PICT 2010 N° 647), Secretaría de Ciencia y Técnica-Universidad Nacional de Córdoba (SeCyT-UNC), Consejo Nacional de Investigaciones Científicas y Tecnológicas de Argentina (CONICET), Ministerio de Ciencia y Técnica de Córdoba, Fundación Antorchas and Florencio Fiorini.

Supplementary material available online

Supplementary Table 1 and Figure 1

Notice of Correction:

Corrections have been made to the author names in the running head and correspondence address since this article’s original online publication date of September 12, 2014.