Oxysterols as Endogenous Lipid Toxins and Toxic Signaling Mediators in Chronic Disease

Oxysterols, oxygenated derivatives of cholesterol, have emerged as critical regulators of metabolic homeostasis and interorgan communication. Generated via enzymatic and oxidative pathways, they function as ligands for nuclear receptors such as liver X receptors (LXRs) and modulators of GPCR signaling. Through these mechanisms, oxysterols integrate lipid metabolism with glucose regulation, inflammation, and immune responses across key metabolic organs, including liver, adipose tissue, brain, and pancreas. Notably, the oxysterol-LXR axis coordinates cholesterol flux with insulin sensitivity and glycemic control, while dysregulated oxysterol accumulation promotes cellular stress and chronic disease. These insights position oxysterols as promising therapeutic targets in metabolic disorders.