POLYPHENOLIC FRACTIONS FROM CITRUS BERGAMIA LEAVES AND FRUIT ATTENUATE PARAMETERS OF WESTERN DIET-INDUCED METABOLIC SYNDROME IN RATS

Abstract: Metabolic syndrome (MetS) is a major public health problem, with an estimated prevalence of 20% to 25% worldwide. It is characterized by a cluster of metabolic abnormalities associated with excess adiposity, including insulin resistance, hyperglycemia, systemic arterial hypertension, and dyslipidemia. Its development is associated with the chronic consumption of a Western diet (WD), which is rich in refined sugars and saturated fats. In this context, plant-derived bioactive compounds have been associated with the attenuation of MetS-related alterations. Bergamot (Citrus bergamia) is notable for its high phenolic compounds and scientific interest. Both leaves (Le) and fruit (Fr) contain flavanones and derivatives linked to antioxidant, anti-inflammatory, lipid-lowering, and glucose-lowering effects. While benefits of polyphenolic fractions from leaves and fruit are reported, their specific effects on MetS remain unclear.This study aimed to compare the effects of polyphenolic fractions obtained from Citrus bergamia leaves and fruit on parameters of Western diet-induced metabolic syndrome in rats. Male Wistar rats (±180 g) were initially randomized into two experimental groups and received, ad libitum, either a control diet (C, n=10) or a WD combined with 25% sucrose in drinking water (WD, n=30) for 20 weeks to induce MetS (CEUA 1470/2025). Subsequently, the animals were redistributed into four experimental groups: C (n=10), WD + vehicle (n=10), WD + Le (n=10), and WD + Fr (n=10). The leaf fraction was administered at 50 mg/kg/day, and the fruit fraction at 250 mg/kg/day, both by oral gavage for 10 weeks. After this period, the animals were euthanised and the plasma and adipose tissue were collected for analysis. MetS was assessed by body weight (g), adiposity index (%), systolic blood pressure (mmHg), fasting glucose (mg/dL), insulin resistance by TyG, and plasma triglyceride concentrations (mg/dL). Data normality was assessed using the Shapiro–Wilk test. Groups were compared by one-way ANOVA/Tukey’s test or by Kruskal–Wallis/Dunn’s test. After 20 weeks, the WD group showed an increase in body weight, adiposity index, SBP, blood glucose, TyG, and triglycerides compared to the C group (p<0.001), confirming the development of MetS.Treatment with both fractions attenuated WD-induced MetS alterations. Both the leaf and fruit fractions reduced body weight, adiposity index, blood pressure, and insulin resistance (p<0.05), although the leaf fraction produced a greater reduction in body weight (WD+Le=445.61±27.50 vs. WD=524.56±36.85; p<0.001; WD+Fr=490.08±23.48 vs. WD=524.56±36.85; p=0.038). Only the fruit fraction significantly reduced fasting blood glucose [WD+Fr=99.50 mg/dL (99.38–101.50) vs. WD=107.00 mg/dL (106.00–109.50); p=0.033] and serum triglyceride levels [WD+Fr=110.10 mg/dL (107.17–113.56) vs. WD=165.60 mg/dL (136.44–187.23); p=0.007]. Both fractions attenuated Western diet-induced MetS alterations, although they exhibited distinct effects. The leaf fraction had a greater effect on body weight, whereas the fruit fraction exerted broader effects on metabolic and cardiovascular parameters.

FAPESP Processo 2026/07453-0