**Background:** Longan (Dimocarpus longan Lour.) is a fruit widely cultivated in Southeast Asia and Southern China, where it has been used in traditional Chinese medicine. The pericarps and seeds, accounting for approximately 30% of the fresh fruit weight, are typically discarded as waste. Previous studies have shown these byproducts are rich in phenolic compounds with various biological activities, but their effect on lipid metabolism had not been investigated. Abnormal lipid metabolism is a key risk factor for obesity, hyperlipidemia, fatty liver, and type 2 diabetes. The nuclear receptors PPARα and LXRα play important regulatory roles in lipid homeostasis and represent targets for dietary interventions.
**Methods:** Longan byproducts (pericarps and seeds of the Chuliang cultivar) were collected, freeze-dried, ground, and extracted with 80% aqueous ethanol, followed by ethyl acetate re-extraction. The phenolic profile was analyzed using UPLC-QqQ-MS/MS. Total phenolic content was measured by the Folin–Ciocalteu method. Antioxidant activity was assessed via DPPH, ABTS, and FRAP assays. For the in vivo study, male C57BL/6J mice were randomly divided into three groups (n=8 per group): Chow diet (10% calories from fat), high-fat diet (HFD, 60% calories from fat), or HFD plus 0.2% LPPE for 12 weeks. Body weight and food intake were recorded weekly. Serum lipids (TC, TG, HDL-c, LDL-c), liver lipids, and histological changes (H&E and Oil Red O staining) were evaluated. Gene expression (PPARα, LXRα, FAS, CYP7A1, CYP27A1) was measured by RT-PCR, and protein expression (PPARα, LXRα, FAS, CYP7A1) by Western blot.
**Key Results:** The extraction rate of LPPE was 10.69%, and total phenolic content was 285.350 ± 36.430 mg GAE/g. Eleven phenolic compounds were identified, with the principal components being phlorizin (38.894 ± 3.765 mg/g), proanthocyanidin A2 (24.382 ± 2.859 mg/g), gallic acid (24.080 ± 2.791 mg/g), and epicatechin (7.592 ± 0.231 mg/g). Antioxidant activities were 231.350 ± 21.640 (DPPH), 252.380 ± 31.150 (ABTS), and 558.220 ± 59.810 (FRAP) mg Vc/g. In the animal study, HFD led to more than 60% higher body weight compared to the Chow group after 12 weeks. LPPE supplementation caused a mean 11.8% reduction in total body weight compared to the HFD group without affecting food intake. LPPE significantly reduced serum TC, TG, HDL-c, and LDL-c levels compared to the HFD group. Liver TG and TC contents were also markedly reduced by LPPE. Histological analysis showed that HFD induced excessive ballooning degeneration and lipid droplets in the liver, which were strongly ameliorated by LPPE treatment. Gene expression analysis revealed that HFD significantly decreased PPARα and LXRα expression, while LPPE significantly enhanced both. FAS gene expression was increased in the HFD group and inhibited by LPPE. CYP7A1 and CYP27A1 expression were decreased in the HFD group and upregulated by LPPE. Western blot analysis confirmed these findings at the protein level for PPARα, LXRα, FAS, and CYP7A1.
**Clinical Implications:** This study provides the first evidence that longan byproduct polyphenol extracts can improve lipid metabolism disorders in a high-fat diet mouse model, likely through the PPARα/LXRα/FAS/CYP7A1 pathway. The findings support the potential use of LPPE as a dietary supplement for managing obesity, hyperlipidemia, and hepatic steatosis. Given that longan byproducts are currently discarded as waste, their valorization as a source of bioactive polyphenols offers both economic and environmental benefits. However, the specific compounds responsible for the observed effects and their synergistic interactions require further investigation. Human clinical studies are needed to confirm the efficacy and safety of LPPE supplementation in humans.