Foreword

Lipid mediators are a class of bioactive lipids that are locally biosynthesized in response to extracellular stimuli, and secreted extracellularly. They then transmit signals to their target cells via binding to their specific receptors. Among lipid mediators, eicosanoids such as prostaglandins (PGs), thromboxane and leukotrienes (LTs), which are derived from eicosapolyenoic acids including arachidonic acid, were identified in the 1960 s and 1970 s and could be called the first generation of lipid mediators. Eicosanoids have been shown to be involved in various kinds of physiological and pathological processes, and have been characterized as attractive drug targets. Forty years ago, in 1982, Drs. Bergström, Samuelsson, and Vane won the Nobel Prize in Physiology or Medicine for their discoveries concerning PGs and related biologically active substances. In addition to eicosanoids, lysophospholipids and their related compounds have been identified as second-generation lipid mediators and they are also now attracting attention for potential drug discovery applications. Moreover, high-sensitivity LC/MS recently revealed the existence of third-generation lipid mediators derived from ω3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Many of these ω3 PUFA-derived lipid mediators have been shown to function as specialized pro-resolving mediators (SPMs).

After the discoveries of these lipid mediators, various kinds of their biosynthetic and degradation enzymes and receptors have been identified. Unlike proteins, whose information can be readily obtained from the genome, we cannot directly read the information of lipid mediators from the genome since they are not genome-encoded. However, we can follow the dynamics and functions of these lipid mediators indirectly by investigating their biosynthetic enzymes and receptors. Recent research on these enzymes and receptors using pharmacological and genetic approaches has uncovered the emerging roles of individual lipid mediators in health sciences and further supports the potential of individual biosynthetic enzymes and receptors as novel drug targets.

In the first half of this Current Topics section, Prof. Fujimori, Dr. Inazumi and Prof. Sugimoto, and ourselves reviewed the emerging roles of PGs in inflammatory and metabolic diseases. We reviewed the novel functions of PGI₂ synthase in inflammatory reactions. Prof. Fujimori introduced the roles of PGD₂ and PGF_2α synthases in adipogenesis. Dr. Inazumi and Prof. Sugimoto summarized the functions of PGE₂ and the other prostanoid receptors in adipocytes. Next, Prof. Arita and his colleagues summarized the roles of PGs and other PUFA-derived lipid mediators, which include novel ω3 PUFA-derived mediators, in epithelial homeostasis. Finally, Prof. Aoki and his colleagues overviewed the history of the advances made in our understanding of lysophospholipids. In their review, they highlighted that many of the advances in research on lysophospholipids have been made by Japanese pharmaceutical scientists. The contributions of Japanese pharmaceutical scientists, including the authors in this Current Topics, to advances in research on lipid mediators such as PGs, LTs, and SPMs, as well as lysophospholipids have also been great.

I believe that these reviews provide an intimate understanding of recent advances in research on lipid mediators, and hope that young Japanese researchers will join this research field and further develop it in the future. As the editor of this Current Topics, I sincerely thank all the authors for their valuable contributions.