Central nervous system adaptation mechanism of obesity induced by high-fat high-sucrose diet: Differences in brain function between obese and obese resistant rats based on fMRI.

Objective: The prevalence of metabolic obesity continues to rise, yet its pathogenesis remains controversial. This study focuses on the central neural regulatory differences underlying phenotypic divergence between diet-induced obese (OB) and obesity-resistant (OR) rats following long-term high-fat and high-sucrose diet (HFHSD) exposure. Methods: Forty male Wistar rats were randomized to normal diet group (ND,n = 8) or HFHSD group (n = 32). After 8 weeks, HFHSD rats were split into OB (n = 7) and OR (n = 8) by weight. OB/OR continued HFHSD for 8 weeks with food intake recorded. At week 15, OGTT and functional magnetic resonance imaging (fMRI)-derived amplitude of low-frequency fluctuations (ALFF) were performed. At week 16, metabolic and somatic parameters were measured. Results: Compared to the OR group, OB rats exhibited persistent hyperphagia, elevated triglycerides, TyG index, and leptin levels, significantly increased liver, heart, and kidney masses, and impaired glucose tolerance (all Conclusion: Long-term HFHSD induces functional remodeling of the hindbrain-RSC circuit in obese rats, and this neuroplastic alteration is closely associated with systemic metabolic burden, suggesting its involvement in the pathophysiology of obesity.