Abstract
Ether lipids are a unique class of glycero- and glycerophospho-lipid that carry an ether or vinyl ether linked fatty alcohol at the sn-1 position of the glycerol backbone. These specialised lipids are important endogenous anti-oxidants with additional roles in regulating membrane fluidity and dynamics, intracellular signalling, immunomodulation and cholesterol metabolism. Lipidomic profiling of human population cohorts has identified new associations between reduced circulatory plasmalogen levels, an abundant and biologically active sub-class of ether lipids, with obesity and body-mass index. These findings align with the growing body of work exploring novel roles for ether lipids within adipose tissue. In this regard, ether lipids have now been linked to facilitating lipid droplet formation, regulating thermogenesis and mediating beiging of white adipose tissue in early life. This review will assess recent findings in both population studies and studies using cell and animal models to delineate the functional and protective roles of ether lipids in the setting of obesity. We will also discuss the therapeutic potential of ether lipid supplementation to attenuate diet-induced obesity.
Highlights
Specialty section: This article was submitted to Lipid and Fatty Acid Research, a section of the journal Frontiers in Physiology
Ether lipids are a unique class of glycero- and glycerophospho-lipid that carry an ether or vinyl ether linked fatty alcohol at the sn-1 position of the glycerol backbone
Following on from their early work, Pietiläinen et al (2011) performed lipidomic analysis on the subcutaneous WAT (SAT) of healthy and morbidly obese weight-discordant twins (Pietiläinen et al, 2011). They demonstrated that unlike in the obese twins, remodelling of polyunsaturated fatty acids (PUFA)-plasmalogens was considerably reduced in the morbidly obese twins. These findings suggest that the protective adaptations induced by the onset of obesity are lost as adiposity increases
Summary
Ether lipids are a unique class of peroxisome-derived glycero- and glycerophospho-lipid They carry an ether or vinyl ether linked fatty alcohol at the sn-1 position, and an ester linked fatty acid either at the sn-2 position (ether phospholipids), or at both the sn and sn-3 positions (ether glycerolipids). Ether lipids are highly abundant molecules that account for around 20% of the total phospholipid content in mammalian cells (Nagan and Zoeller, 2001; Paul et al, 2019) They make up a significant component of subcellular membranes, including the membranes of the nucleus, endoplasmic reticulum (ER), post-Golgi network and mitochondria (Nagan and Zoeller, 2001; Honsho et al, 2008). These lipids contain varying structural and physicochemical properties, including different head groups and fatty acyl chains.
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