Roles of polyunsaturated fatty acids, from mediators to membranes

Abstract

Polyunsaturated fatty acids (PUFAs), such as arachidonic acid and docosahexaenoic acid, are recognized as important biomolecules, but understanding their precise roles and modes of action remains challenging. PUFAs are precursors for a plethora of signaling lipids, for which knowledge about synthetic pathways and receptors has accumulated. However, due to their extreme diversity and the ambiguity concerning the identity of their cognate receptors, the roles of PUFA-derived signaling lipids require more investigation. In addition, PUFA functions cannot be explained just as lipid mediator precursors, since they are also critical for the regulation of membrane biophysical properties. The presence of PUFAs in membrane lipids also affects the functions of transmembrane proteins and peripheral membrane proteins. Although the roles of PUFAs as membrane lipid building blocks were difficult to analyze, the discovery of lysophospholipid acyltransferases, which are critical for their incorporation, advanced our understanding. Recent studies unveiled how lysophospholipid acyltransferases affect PUFA levels in membrane lipids, and their genetic manipulation became an excellent strategy to study the roles of PUFA-containing lipids. In this review, we will provide an overview of metabolic pathways regulating PUFAs as lipid mediator precursors and membrane components, and update recent progress about their functions. Some issues to be solved for future research will also be discussed.

Mapping membrane lipids in the developing and adult mouse retina under physiological and pathological conditions using mass spectrometry

“…Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) exert antiangiogenic and neuroprotective functions in the retina ( 6 ). The LC-PUFA docosahexaenoic acid (DHA) plays a pivotal role in photoreceptor development and maintenance ( 7 , 8 ). High intake of eicosapentaenoic acid (EPA) and DHA has been shown to prevent or delay intermediate age-related macular degeneration.…”

Inadequate Content of Docosahexaenoic Acid (DHA) of Donor Human Milk for Feeding Preterm Infants: A Comparison with Mother’s Own Milk at Different Stages of Lactation

“…DHA is derived from ALA through the enzymatic biosynthesis; ALA along with its omega-6 counterpart LA must be obtained from the diet because the human body is unable to synthesize them. PUFAs have shown to exert pleiotropic effects on cell membranes and to play a crucial role for the regulation of membrane biophysical properties, particularly as lipid mediator precursors and membrane components especially n-3 PUFAs [ 2 , 3 ]. DHA has demonstrated consistent beneficial healthy effects, including anti-inflammatory, antiproliferative, antiangiogenic, and antioxidant properties [ 4 , 5 , 6 ], as well as a critical involvement on underlying mechanisms of fetal neurodevelopment and immune function of newborns [ 7 , 8 ].…”

Hepatic Levels of DHA-Containing Phospholipids Instruct SREBP1-Mediated Synthesis and Systemic Delivery of Polyunsaturated Fatty Acids

“…Recent studies have shown that besides their quantity, the qualities of fatty acids (e.g., saturated fatty acid toxicity and omega-3/omega-6 fatty acid balance) are involved in various human diseases, including metabolic syndrome, inflammatory diseases, and neuronal diseases ( Bazinet and Laye, 2014 ; Estadella et al., 2013 ). Especially, omega-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), and omega-6 PUFAs, including arachidonic acid (ARA), are implicated in diverse cellular processes and in the progression of these diseases as bioactive lipid mediators, or as components of membrane phospholipids (PLs) ( Harayama and Shimizu, 2020 ; Jump et al., 2013 ; Milligan et al., 2017 ; Shimizu, 2009 ; Wang and Tontonoz, 2019 ). PUFA-containing PLs are supposed to affect the membrane-based cellular processes, such as endo/exocytosis, and localization and functions of a number of membrane proteins by providing fluidity to the cellular membrane ( Antonny et al., 2015 ; Harayama and Riezman, 2018 ).…”