Exploiting oxidized lipids and the lipid-binding GPCRs against cardiometabolic diseases

Lipids govern vital cellular processes and drive physiological changes in response to different pathological or environmental cues. Lipid species can be roughly divided into structural and signalling lipids. The former is essential for membrane composition, while the latter are usually oxidized lipids. These mediators provide beneficial effects against cardiometabolic diseases (CMDs), including fatty-liver diseases, atherosclerosis, thrombosis, obesity, and Type 2 diabetes. For instance, several oxylipins were recently found to improve glucose homeostasis, increase insulin secretion, and inhibit platelet aggregation, while specialized pro-resolving mediators (SPMs) are able to ameliorate CMD by shaping the immune system. These lipids act mainly by stimulating GPCRs. In this review, we provide an updated and comprehensive overview of the current state of the literature on signalling lipids in the context of CMD. We also highlight the network encompassing the lipid-modifying enzymes and the lipid-binding GPCRs, as well as their interactions in health and disease.