Cold-induced phosphatidylethanolamine synthesis in liver and brown adipose tissue of mice

Abstract

Increasing energy expenditure in brown adipose (BAT) tissue by cold-induced lipolysis is discussed as a potential strategy to counteract imbalanced lipid homeostasis caused through unhealthy lifestyle and cardiometabolic disease. Yet, it is largely unclear how liberated fatty acids (FA) are metabolized. We investigated the liver and BAT lipidome of mice housed for 1 week at thermoneutrality, 23 °C and 4 °C using quantitative mass spectrometry-based lipidomics. Housing at temperatures below thermoneutrality triggered the generation of phosphatidylethanolamine (PE) in both tissues. Particularly, the concentrations of PE containing polyunsaturated fatty acids (PUFA) in their acyl chains like PE 18:0_20:4 were increased at cold. Investigation of the plasma's FA profile using gas chromatography coupled to mass spectrometry revealed a negative correlation of PUFA with unsaturated PE in liver and BAT indicating a flux of FA from the circulation into these tissues. Beta-adrenergic stimulation elevated intracellular levels of PE 38:4 and PE 40:6 in beige wildtype adipocytes, but not in adipose triglyceride lipase (ATGL)-deficient cells. These results imply an induction of PE synthesis in liver, BAT and thermogenic adipocytes after activation of the beta-adrenergic signaling cascade.