Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2021.094
Specialized Proresolving Mediators for Therapeutic Interventions Targeting Metabolic and Inflammatory Disorders
Yong-Hyun Han1, Kyeongjin Lee1, Abhirup Saha2, Juhyeong Han2, Haena Choi2, Minsoo Noh2, Yun-Hee Lee2,* and Mi-Ock Lee2,3,*
1Laboratory of Pathology and Physiology, College of Pharmacy, Kangwon National University, Chuncheon 24341,
2College of Pharmacy, Seoul National University, Seoul 08826,
3Bio-MAX Institute, Seoul National University, Seoul 08826, Republic of Korea
*E-mail: molee@snu.ac.kr (Lee MO), yunhee.lee@snu.ac.kr (Lee YH)
Tel: +82-2-880-9331 (Lee MO), +82-2-880-2139 (Lee YH)
Fax: +82-2-888-9122 (Lee MO), +82-2-888-9122 (Lee YH)
Received: May 18, 2021; Revised: June 7, 2021; Accepted: June 8, 2021; Published online: June 24, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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 metabolism 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.
Keywords: Specialized pro-resolving mediators, Resolvins, Maresins, NAFLDs, Adipose tissue


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