Specialized Proresolving Mediators for Therapeutic Interventions Targeting Metabolic and Inflammatory Disorders
10.4062/biomolther.2021.094
- Author:
Yong-Hyun HAN
1
;
Kyeongjin LEE
;
Abhirup SAHA
;
Juhyeong HAN
;
Haena CHOI
;
Minsoo NOH
;
Yun-Hee LEE
;
Mi-Ock LEE
Author Information
1. Laboratory of Pathology and Physiology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
- Publication Type:Review
- From:Biomolecules & Therapeutics
2021;29(5):455-464
- CountryRepublic of Korea
- Language:English
-
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.
