Targeted Lipidomics Reveals Citrus aurantifolia Peel Extract's Potential to Increase Lipid Catabolism With PC34:1 as a Discriminative Metabolite.

Regulating lipid metabolism is the main mechanism of exercise to control blood lipids, body weight, and prevent metabolic diseases. However, the effects of complex mixtures of phytochemicals, particularly from plant-derived extracts, on lipid metabolism remain poorly understood. Recently, we developed a green extraction method for lime (Citrus aurantifolia) peel, yielding an extract rich in three major compounds (hesperidin, limonin, and bergaptol). In this study, the effect of the extract on lipid metabolism was investigated in normal human hepatocytes (THLE-2) using a targeted lipidomics approach under nontoxic conditions. The results showed significant increases in 75 lipid metabolites and decreases in four metabolites (propenoylcarnitine [C3:1], octadecadienylcarnitine [C18:2], PC 42:1, and dodecenoylcarnitine). Interestingly, metabolites showing ≥ 2-fold changes were exclusively acylcarnitines, with increases in medium-chain acylcarnitines (C12 and C6:1) and a decrease in long-chain acylcarnitine (C18:2), consistent with altered fatty acid metabolism. A significant fourfold decrease in C3:1 indicates reduced conversion of branch-chain amino acids (isoleucine) to fatty acid intermediates. PCA, PLS-DA, and OPLS-DA analyses consistently identified phosphatidylcholine 34:1 (PC34:1) as the key metabolite distinguishing the treated and control groups, based on VIP score. Taken together, the findings suggest that lime peel extract may reduce lipid synthesis from amino acids and may promote lipid catabolism in hepatocyte cell models with a dominant medium-chain acylcarnitine pattern, and PC34:1 as the discriminative metabolite associated with treatment response. This novel functional ingredient may have potential implications in preventing dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD), warranting further in vivo and clinical studies.