Oxysterols as Regulators of Inter-Organ Metabolic Communication: Molecular Mechanisms, Disease Associations, and Vulnerable Populations.

Oxysterols, oxygenated derivatives of cholesterol, are emerging as pivotal regulators of lipid metabolism, cellular communication, and immune responses. Their increased polarity enables rapid intermembrane transport and dynamic signaling functions, distinguishing them from cholesterol. Produced through both enzymatic (cytochrome P450 mediated) and non-enzymatic (oxidative stress-driven) pathways, oxysterols influence cholesterol homeostasis, membrane dynamics, inflammation, apoptosis, and proliferation. While essential for physiological balance, pathological accumulation of specific oxysterols, such as 7-ketocholesterol (7-KC) and 27-hydroxycholesterol (27-HC), contributes to atherosclerosis, neurodegeneration, and cancer. Dietary intake, hypercholesterolemia, obesity, aging, and genetic predispositions elevate oxysterol levels, increasing disease risk. This review highlights their dual roles as metabolic regulators and pathogenic agents, underscoring the importance of targeting oxysterol pathways for novel diagnostic and therapeutic strategies.