POWDER BERGAMOT JUICE AS A BIOACTIVE STRATEGY AGAINST HEPATIC LIPID ACCUMULATION AND OXIDATIVE STRESS IN DIET-INDUCED MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive hepatic lipid accumulation and is closely associated with obesity, oxidative stress, and liver injury. Changes in hepatic fatty acid composition may further contribute to disease progression. Powder bergamot juice (PBJ), rich in flavonoids such as neoeriocitrin, naringin, and neohesperidin, has metabolic, antioxidant, and hepatoprotective potential. However, its effects on hepatic lipid metabolism, oxidative status, and fatty acid composition after MASLD establishment remain poorly understood. This study evaluated the therapeutic effects of PBJ on MASLD-related parameters, hepatic lipid profile, oxidative markers, and fatty acid composition in diet-induced MASLD rats. Male Wistar rats were fed either a control diet (n=9) or a high sugar-fat diet (HSFD; n=18) for 20 weeks, to induce MASLD. MASLD experimental model was characterized by body weight (BW), plasma triglycerides (TG), systolic blood pressure (SBP), glycemia (p<0.001). Subsequently, animals were allocated to Control, MASLD and MASLD+PBJ, with PBJ administered by gavage at 250mg/Kg/day for 10 weeks, CEUA1470. At the end of treatment, MASLD-related parameters and oxidative markers were assessed: BW, adiposity index (AI), plasma TG, SBP, ALT activity, protein carbonylation (PC), and catalase (CAT) activity. Even as, lipid profile was evaluated by TG, cholesterol, fatty acids were quantified in liver. Data were analyzed by one-way ANOVA followed by Tukey’s post-hoc test, adopting p<0.05. Compared with Control, MASLD exhibited increased MASLD-related parameters, including BW (518.4±43.2 vs. 455.3±19.6; p=0.003), AI (9.9±2.7 vs. 5.4±1.1%; p<0.001), ALT activity (88.8±19.8 vs. 63.8±12.9 U/L; p=0.008), TyG index (4.7±0.1 vs. 4.2±0.1; p<0.001), and hepatic lipid accumulation by Oil Red O staining (12.5±7.0 vs. 0.3±0.3 % lipids per area; p<0.001). Regarding the hepatic lipid profile, MASLD showed increased HTG (244.2±53.3 vs. 56.4±15.6 mg/g; p<0.001), hepatic cholesterol (90.0±18.4 vs. 52.6±13.7 mg/g; p<0.001), and reduced cis-11-eicosenoic acid (2282,3±938,6 vs. 28580,7±6148,3 area; p<0.001), cis-5,8,11,14,17-eicosapentaenoic acid (592,9±66,2 vs. 628560,2±97190,2 area; p<0.001) and nervonic acid (16227,7±5780,1 vs. 47747,0±10606,4 area; p=0.002). Oxidative markers indicated increased PC (2.7±0.7 vs. 2.2±0.5 nmol/mg protein; p=0.003), and reduced CAT activity (11.3±2.3 vs. 13.8±1.1 U/g protein; p=0.049). Compared with MASLD, PBJ-treated animals exhibited reduced ALT activity (64.3±15.2 vs. 88.8±19.8 U/L; p=0.010). In the hepatic lipid profile, PBJ reduced HTG (134.0±52.5 vs. 244.2±53.3 mg/g; p<0.001), hepatic cholesterol (55.1±13.4 vs. 90.0±18.1 mg/g; p<0.001), while increased hepatic cis-11-eicosenoic acid (4763,9±717,4 vs. 2282,3±938,6 area; p<0.001), cis-5,8,11,14,17-eicosapentaenoic acid (23614,7±8578,1 and 592,9±66,2 area; p<0.001), and nervonic acid (61160,3±11074,3 vs. 16227,7±5780,1 area; p=0.001). For oxidative markers, PBJ reduced PC (1.9±0.4 vs. 2.7±0.7 nmol/mg protein; p<0.001) and increased CAT activity (15.0±4.0 vs. 11.3±2.3 U/g protein; p=0.040). Notably, these effects occurred without reductions in BW or AI. PBJ improved hepatic lipid metabolism, oxidative balance, and fatty acid composition in diet-induced MASLD, supporting its potential as a dietary strategy for targeting hepatic metabolic dysfunction. FAPESP 2021/13050-2.