PPARs at the crossroads of lipid signaling and inflammation

Nuclear receptors (NRs) are ligand-dependent transcription factors whose activation affects genes controlling vital processes. Among them, the peroxisome proliferator-activated receptors (PPARs) have emerged as links between lipids, metabolic diseases, and innate immunity. PPARs are activated by fatty acids and their derivatives, many of which also signal through membrane receptors, thereby creating a lipid signaling network between the cell surface and the nucleus. Tissues that play a role in whole-body metabolic homeostasis, such as adipose tissue, liver, skeletal muscle, intestines, and blood vessel walls, are prone to inflammation when metabolism is disturbed, a complication that promotes type 2 diabetes and cardiovascular disease. This review discusses the protective roles of PPARs in inflammatory conditions and the therapeutic anti-inflammatory potential of PPAR ligands. Nuclear receptors (NRs) are ligand-dependent transcription factors whose activation affects genes controlling vital processes. Among them, the peroxisome proliferator-activated receptors (PPARs) have emerged as links between lipids, metabolic diseases, and innate immunity. PPARs are activated by fatty acids and their derivatives, many of which also signal through membrane receptors, thereby creating a lipid signaling network between the cell surface and the nucleus. Tissues that play a role in whole-body metabolic homeostasis, such as adipose tissue, liver, skeletal muscle, intestines, and blood vessel walls, are prone to inflammation when metabolism is disturbed, a complication that promotes type 2 diabetes and cardiovascular disease. This review discusses the protective roles of PPARs in inflammatory conditions and the therapeutic anti-inflammatory potential of PPAR ligands. anti-inflammatory drug used to treat ulcerative colitis and Crohn's disease. a fatty acid resulting from the non-enzymatic oxidation of linoleic acid. a lipoxygenase-activating hydroperoxide non-enzymatically derived from linoleic acid through the action of reactive oxygen species. a product of 13-HODE by a NAD+-dependent dehydrogenase. a major arachidonic acid metabolite from the 15-lipoxygenase pathway. a polyunsaturated FA, produced by the action of 15-lipoxygenase on arachidonic acid, that mediates the activation of activator protein-1. an n-6 polyunsaturated fatty acid present in membrane phospholipids that is involved in cellular signaling as a lipid second messenger. also known as M2, AAMs promote angiogenesis and tissue repair, and produce anti-inflammatory cytokines. a heterodimeric transcription factor that controls differentiation, proliferation, and apoptosis. also known as M1, CAMs are immune effector cells that are proinflammatory and fight infection. Also termed cluster of differentiation 36 (CD36), is a long-chain fatty acid transporter that is present at the plasma membrane. these cells assist other white blood cells in immunologic processes, including B-cell maturation and the activation of cytotoxic T cells and macrophages. cells found in the perisinusoidal space and involved in liver fibrosis. a group of inflammatory conditions of the colon and small intestine, including ulcerative colitis and Crohn's disease. IECs cover the small and large intestines. They take part in digestion and immunity, and function as a barrier and a first-line pathogen recognition system. an inhibitor of NF-κB. cytokines involved in inflammation and the regulation of the immune system. a polyunsaturated n-6 fatty acid used in the biosynthesis of AA and some prostaglandins. immune response-triggering molecules found in the outer membrane of Gram-negative bacteria. anti-inflammatory FAs containing a double bond at the third carbon atom from the end of the carbon chain. a mitochondrial process that produces ATP through the oxidation of nutrients also known as suppressor T cells, Tregs are specialized to actively suppress immune activation. compounds synthesized by the human body from EPA and DHA, via the COX-2 pathway. Resolvins are nonclassic eicosanoids that reduce cellular inflammation by inhibiting the production and transportation of inflammatory cells and chemicals to the sites of inflammation. a post-translational modification that modulates functions such as nuclear–cytosolic transport, transcriptional regulation, and protein stability.