Beyond the essential oil: Citrus bergamia juice powder attenuates the integrated injury of a Western diet

Abstract: Citrus bergamia juice powder (CB), a bioactive-rich co-product generated during the industrial processing of bergamot after essential oil extraction, represents a promising opportunity for the valorization of an otherwise underutilized fraction of the fruit. Beyond its potential as a source of flavonoids and other bioactive compounds, its biological effects on the integrated metabolic response to a Western diet (WD) remain to be elucidated. A WD, rich in sugar and fat, disrupts systemic and skeletal muscle homeostasis and promotes metabolic, inflammatory, and oxidative alterations. However, existing studies have largely focused on isolated biomarkers, providing limited insight into the broader and interconnected metabolic effects of CB treatment. This study aimed to determine whether CB attenuates the integrated systemic and skeletal muscle injury induced by a WD. Male Wistar rats (CEUA 1476/2025) received a control diet or WD for 20 weeks. At week 20, rats were allocated to four groups: control (C), control + CB (C+CB), WD, and WD + CB (n=7/group). CB was administered by gavage (250 mg/kg/day) for 10 weeks. Systemic and quadriceps muscle parameters related to body composition, blood pressure, glucose and lipid metabolism, oxidative damage, inflammation, and insulin/redox signaling were assessed. Composite z-scores were generated for global, metabolic, inflammatory, and oxidative-damage domains, followed by two-way ANOVA and principal component analysis (PCA). The WD increased the global metabolic dysfunction score and altered metabolic, inflammatory, and oxidative-damage domains compared with C (all p<0.01). CB reduced the global score in WD rats (p<0.001), as well as metabolic (p=0.006), inflammatory (p=0.006), and oxidative-damage (p=0.025) scores. Notably, inflammatory and oxidative-damage scores no longer differed from C after CB treatment. PCA further revealed a distinct redox-related pattern associated with CB treatment, with separation of WD+CB from WD characterized by NRF-2 and KEAP-1 loadings opposite to those of MDA, protein carbonyl, and muscle triglycerides (p<0.001). CB increased muscle NRF-2 in WD rats (p=0.027), and NRF-2 was inversely correlated with HOMA-IR (rs=−0.74, p=0.002) and MDA (rs=−0.61, p=0.020). In control rats, CB did not significantly alter any composite score. Overall, CB attenuated the integrated systemic and skeletal muscle injury induced by the WD, particularly inflammatory and oxidative alterations, and was associated with increased muscle NRF-2 and lower oxidative damage. These findings suggest that modulation of redox signaling may contribute to the effects of Citrus bergamia juice powder in attenuating diet-induced systemic and skeletal muscle injury.

Acknowledments: FAPESP 2024/00750-4