Metabolic Modulation by Butin: Protection Against High-Fat Diet-Induced Obesity in Rats via Antioxidants/Oxidative Stress/Hormonal Regulation/Lipid Metabolism/FGF15 Signaling Pathway

Background: Obesity is a polyetiological condition characterized by excessive adiposity, resulting from a disequilibrium between energy intake and energy expenditure. High-fat diets (HFDs) have been identified as key drivers of the obesity epidemic and its comorbidities. Butin, a natural flavonoid with antioxidant and oxidative stress-modulating properties, has been proposed as a potential therapeutic agent for obesity. This study investigated the efficacy of butin against HFD-induced obesity in rats. Methods: Thirty Wistar rats were orally administered butin diluted with 0.5% sodium carboxymethyl cellulose for 30 days. The rats were randomly divided into five groups: typical diet, HFD control, HFD + 10 mg/kg butin, HFD + 20 mg/kg butin, and 20 mg/kg butin alone. At the end of the study, biochemical parameters including lipid profile [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL)], liver function test [alanine aminotransferase (ALT), aspartate aminotransferase (AST)], kidney test [creatinine, blood urea nitrogen (BUN)], free fatty acid (FFA), as well as antioxidant activity [superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and malonaldehyde (MDA)], were performed. Furthermore, pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], concentrations of serum insulin, leptin, ghrelin, adiponectin (ADP), and fibroblast growth factor 15 (FGF15) were also evaluated. Results: Butin exhibited substantial efficacy in mitigating HFD-induced obesity in rats. Butin administration resulted in a statistically significant reduction in the levels of TG, TC, TNF-α, IL-1β, IL-6, MDA, ALT, AST, BUN, and creatinine, while simultaneously elevating the levels of HDL, SOD, GSH, and CAT. Moreover, butin significantly modulated serum insulin, leptin, ghrelin, ADP, FFA, and FGF15 suggesting its potential for managing obesity-related metabolic and inflammatory markers. Analysis of the data revealed that butin treatment could regulate potential biomarkers and other metabolic pathways associated with HFDinduced obesity in rats. Conclusion: Butin may attenuate hyperlipidemia and protect against HFD-induced obesity in rats through a pleiotropic mechanism of action. Additionally, butin may serve as an alternative clinical supplement to ameliorate obesity complications.