Pro-resolving lipid mediators: regulators of inflammation, metabolism and kidney function

Obesity, diabetes mellitus, hypertension and cardiovascular disease are risk factors for chronic kidney disease (CKD) and kidney failure. Chronic, low-grade inflammation is recognized as a major pathogenic mechanism that underlies the association between CKD and obesity, impaired glucose tolerance, insulin resistance and diabetes, through interaction between resident and/or circulating immune cells with parenchymal cells. Thus, considerable interest exists in approaches that target inflammation as a strategy to manage CKD. The initial phase of the inflammatory response to injury or metabolic dysfunction reflects the release of pro-inflammatory mediators including peptides, lipids and cytokines, and the recruitment of leukocytes. In self-limiting inflammation, the evolving inflammatory response is coupled to distinct processes that promote the resolution of inflammation and restore homeostasis. The discovery of endogenously generated lipid mediators - specialized pro-resolving lipid mediators and branched fatty acid esters of hydroxy fatty acids - which promote the resolution of inflammation and attenuate the microvascular and macrovascular complications of obesity and diabetes mellitus highlights novel opportunities for potential therapeutic intervention through the targeting of pro-resolution, rather than anti-inflammatory pathways. Inflammation is a known driver of diabetes and obesity-associated kidney disease. This Review describes the role of endogenous lipid mediators - specialized pro-resolving lipid mediators and branched fatty acid esters of hydroxy fatty acids - in the resolution of inflammation and explores how insights into their function could identify new targets for therapeutic intervention.

Automated summary

Obesity, diabetes mellitus, hypertension, and cardiovascular disease are risk factors for chronic kidney disease and kidney failure. Inflammation is a known driver of diabetes and obesity-associated kidney disease. The discovery of endogenously generated lipid mediators that promote the resolution of inflammation offers novel opportunities for therapeutic intervention.