Investigation of the effects of phase I and II metabolites of D-limonene on lipid metabolism of C57/Bl6 mice

Abstract

Brazil is one of the largest producers and exporters of oranges and orange juice in the world. Among the by-products of this citrus chain, the essential oil of orange peel has great economic value. This oil contains high amounts of the monoterpene D-limonene, to which lipid-lowering effects are attributed, among several actions in different physiological processes. Despite the effects demonstrated in different models, the mechanisms of action of D-limonene on lipid metabolism are not yet well understood. After absorption, xenobiotics undergo molecular modifications and conjugations, generating metabolites that can be eliminated from the body. In general, these metabolites are found in higher concentrations in tissues and biofluids than their parent compound, but know little is known about the bioactivity and the contribution of these molecules to the effects attributed to the parent compound. This project aims at identifying the metabolites generated after the supplementation of D-limonene and relate them to the effects on lipid metabolism attributed to the monoterpene. Male C57/B16 mice will be distributed in 8 groups, 4 of which receiving a low-fat diet and the other 4 groups a high-fat diet. After one week of adaptation, D-limonene will be added to the diets in the concentrations of 0, 0.1, and 0.8%, and the animals will receive these diets for 8 weeks. Urine samples will be collected to analyze D-limonene metabolites that will be correlated with markers of lipid metabolism, in order to identify their biological activity. (AU)