Specialized Proresolving Mediators for Therapeutic Interventions Targeting Metabolic and Inflammatory Disorders

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 omega-3-derived family of molecules, such as resolvins, protectins, and maresins, as well as arachidonic acid-derived (omega-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 ROR alpha. 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.

Automated summary

Uncontrolled inflammation is the basis of many metabolic disorders and can be resolved by specialized proresolving mediators (SPMs) that activate specific receptors and promote resolution of inflammation, microbial clearance, alleviation of pain, and tissue regeneration. Though SPMs have shown potential to attenuate metabolic disorders, the pharmacological aspects and specific receptors and signaling pathways of SPMs are still limited.