Oleic Acid-Esterified Octacosanol as a Functional Ingredient to Counter Obesity-Associated Lipid Dysregulation through PPAR-Targeted Regulation.

Octacosanol, a major constituent of policosanol, exhibits lipid-lowering activity, particularly when esterified with fatty acids. Although its cholesterol-lowering actions have been linked to the modulation of fatty acid and cholesterol biosynthesis, its functions within adipose tissue remain poorly defined. Here, we examined nonesterified octacosanol (NO), lauric acid-esterified octacosanol (LEO), and oleic acid-esterified octacosanol (OEO) in high-fat diet-fed mice for 11 weeks. Target prediction and molecular docking identified PPARα and PPARδ as putative targets of octacosanol, guiding downstream mechanistic analyses in adipose tissue. Both NO and OEO enhanced lipolysis; NO preferentially increased fatty acid β-oxidation, whereas OEO specifically promoted thermogenic remodeling, indicating distinct metabolic consequences driven by ester chemistry. Together, these findings demonstrate that structural modification, particularly oleic acid esterification, substantially augments the metabolic activity of octacosanol in lipid catabolism and thermogenesis, underscoring its potential relevance in obesity-associated metabolic regulation.