Uncontrolled inflammation is considered the pathophysiological basis of many prevalent metabolic disorders, such as nonalcoholic fatty liver disease, diabetes, obesity, and neurodegenerative diseases. The inflammatory response is a self-limiting process that produces a superfamily of chemical mediators, called specialized proresolving mediators (SPMs). SPMs include the ω-3-derived family of molecules, such as resolvins, protectins, and maresins, as well as arachidonic acid-derived (ω-6) lipoxins that stimulate and promote resolution of inflammation, clearance of microbes, and alleviation of pain and promote tissue regeneration via novel mechanisms. SPMs function by binding and activating G protein-coupled receptors, such as FPR2/ALX, GPR32, and ERV1, and nuclear orphan receptors, such as RORα. Recently, several studies reported that SPMs have the potential to attenuate lipid me-tabolism disorders. However, the understanding of pharmacological aspects of SPMs, including tissue-specific biosynthesis, and specific SPM receptors and signaling pathways, is currently limited. Here, we summarize recent advances in the role of SPMs in resolution of inflammatory diseases with metabolic disorders, such as nonalcoholic fatty liver disease and obesity, obtained from preclinical animal studies. In addition, the known SPM receptors and their intracellular signaling are reviewed as targets of resolution of inflammation, and the currently available information on the therapeutic effects of major SPMs for metabolic disorders is summarized.
Bibliographical noteFunding Information:
This study was supported by a grant from the National
This study was supported by a grant from the National Research Foundation of Korea (NRF) (2021R1C1C1004023 to Y.H.H.; NRF-2019R1C1C1002014 to Y.H.L.; 2017R1A2B 3011870 to M.O.L., and 2018R1A5A2024425 to Y.H.L. and M.O.L.) and 2020 Research Grant from Kangwon National University.
© 2021 The Korean Society of Applied Pharmacology.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery