Lipid Mediators in Life Science

Abstract

"Lipid mediators" represent a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. They are exported extracellularly, bind to their cognate G protein-coupled receptors (GPCRs) to transmit signals to target cells, and are then sequestered rapidly through specific enzymatic or non-enzymatic processes. Because of these properties, lipid mediators can be regarded as local hormones or autacoids. Unlike proteins, whose information can be readily obtained from the genome, we cannot directly read out the information of lipids from the genome since they are not genome-encoded. However, we can indirectly follow up the dynamics and functions of lipid mediators by manipulating the genes encoding a particular set of proteins that are essential for their biosynthesis (enzymes), transport (transporters), and signal transduction (receptors). Lipid mediators are involved in many physiological processes, and their dysregulations have been often linked to various diseases such as inflammation, infertility, atherosclerosis, ischemia, metabolic syndrome, and cancer. In this article, I will give an overview of the basic knowledge of various lipid mediators, and then provide an example of how research using mice, gene-manipulated for a lipid mediator-biosynthetic enzyme, contributes to life science and clinical applications.

Sweat lipid mediator profiling: a noninvasive approach for cutaneous research

“…Bioactive lipids come in many forms and regulate a variety of processes, including inflammation, cell growth and differentiation, and vascular homeostasis (14). These mediators, which include oxygenated lipids ("oxylipins"), endocannabinoids, and ceramides, are generally thought to be produced locally via biosynthetic pathways in response to extracellular stimuli and function similarly to local hormones or autacoids (14).…”

Dual Functions of the Trans-2-Enoyl-CoA Reductase TER in the Sphingosine 1-Phosphate Metabolic Pathway and in Fatty Acid Elongation

“…Cells were grown on a plate of SC medium lacking uracil and histidine (SC-His-Ura) or SC-His containing 5-FOA at 30°C for 2 days. B-E, BY4741 (wild type)/pAB119 (3xFLAG-CERS5) cells and ABY80 (tsc13⌬ cells/pAB119) cells were grown in SC-His medium and labeled with 0.07 Ci of [11,12- 2 C, mannosyldiinositol phosphorylceramide. E, lipids were extracted and subjected to trans-methylation.…”

“…Besides being the building blocks of membranes, lipids play many important functions such as acting as lipid mediators and controlling protein activities and cellular signaling by forming lipid microdomains or by covalently or non-covalently binding to specific proteins (1)(2)(3)(4). A balance between synthesis and degradation of each lipid class has to be maintained in these functions to avoid disorders.…”

“…S1P is a well known lipid mediator. Extracellular S1P binds to the cell surface receptors (S1P [1][2][3][4][5] ) and induces several cellular responses, such as proliferation, cell migration, adherent junction assembly, and cytoskeletal remodeling (5,7). In immune systems, S1P plays a pivotal role in the egress of T cells from the thymus and secondary lymphoid tissues.…”

Endocannabinoids and Related Lipids in Chronic Pain: Analytical and Clinical Aspects

“…Various lipid mediators are involved in the regulation of the excitability of peripheral nociceptors [43] and in the mechanisms of inflammation [44]. Lipids belonging to the eicosanoids such as prostaglandins and leukotrienes are the most well-characterized pro-algetic/inflammatory lipid mediators.…”