Powder bergamot juice attenuates skeletal muscle complications in an experimental model of metabolic syndrome

Metabolic syndrome (MetS) promotes skeletal muscle complications, which can impair glucose uptake and contribute to the development of diabetes. In contrast, powder bergamot juice (PBJ) possesses bioactive compounds with potential therapeutic applications. To evaluate the effects of PBJ on skeletal muscle complications in an experimental model of metabolic syndrome. Male Wistar rats were fed a control diet (n=20) or a high-sugar fat diet (n=20) with 25% sucrose in drinking water (w/v) for 20 weeks to induce MetS. After this period, animals were then redistributed into two groups (n=7 each): MetS and MetS + PBJ. PBJ was administered by gavage at 250 mg/kg daily for 10 weeks. Systemic metabolic parameters were measured, and lipid content, fatty acid profile, inflammatory and oxidative stress biomarkers, insulin signaling proteins, and histological outcomes were evaluated in the quadriceps. PBJ treatment significantly attenuated systemic adiposity and dyslipidemia. In the quadriceps, PBJ markedly reduced triglyceride accumulation and modulated the fatty acid composition, lowering saturated fatty acid (SFA) levels and increasing the desaturation index. Oxidative stress markers, including malondialdehyde, advanced oxidation protein products, and protein carbonylation, were reduced, while antioxidant defenses were enhanced by upregulating nuclear factor erythroid 2-related factor 2 (NRF-2) signaling. Pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significantly decreased and interstitial collagen deposition was also attenuated. Crucially, PBJ modulated the endocrine response and increased total protein expression of glucose transporter type 4 (GLUT-4) without altering IRS-1 phosphorylation. PBJ attenuated skeletal muscle complications resulting from MetS. However, due to the absence of a healthy control group, these findings demonstrate an improvement relative to the diseased condition, but cannot confirm a return to a normal physiological baseline. • PBJ reduces intramuscular triglyceride accumulation and promotes qualitative lipid remodeling by increasing the desaturation index (C16:1/C16:0). • The modulation of the fatty acid profile suggests enhanced sarcolemmal membrane fluidity, facilitating glucose transporter dynamics. • Activation of the NRF-2 pathway by PBJ mitigates oxidative stress and suppresses pro-inflammatory cytokines (TNF-α and IL-6) in skeletal muscle. • PBJ attenuates skeletal muscle fibrosis by reducing interstitial collagen deposition, preserving the tissue's structural integrity and metabolic flexibility. • PBJ modulates the endocrine response and upregulates total muscle GLUT-4 expression through an IRS-1-independent pathway.