Caloric restriction and time-restricted feeding differentially modulate metabolic, adipose tissue, and neurobehavioral outcomes in obese rats fed a high-sugar diet

Introduction This study aimed to compare the effects of time-restricted feeding and caloric restriction on glycemic control, adipose tissue IL-6 immunoreactivity, and behavioral outcomes in rats with obesity induced by a high-sugar diet. Methods A total of 40 adult male Wistar rats (approximately 80 days old) were randomized into two groups (initially): a control group (CG, n = 10), fed a standard diet, and an obese group (OG, n = 30), fed a high-sugar diet (HSD) for 13 weeks to induce obesity. Subsequently, animals were randomized into four experimental groups: control (CG, n = 10), obese (OG, n = 10), obese with caloric restriction (OCR, n = 10), and obese with time-restricted feeding (OTRF, n = 10), and subjected to their respective interventions for 4 weeks. Results OCR produced the most pronounced metabolic benefits, significantly reducing body weight, the area under the curve (AUC) of the insulin tolerance test (ITT), insulin resistance, fasting glucose, insulin and leptin levels, adiposity index, adipocyte area, and IL-6 immunopositive area (all p < 0.05), while increasing locomotor and exploratory behavior. Conversely, OTRF primarily modified behavioral outcomes, with increased swimming and reduced immobility in the forced swim test, and also reduced insulin resistance, fasting glucose, insulin and leptin levels (all p < 0.05). OTRF also reduced adipose tissue IL-6 immunoreactivity but did not significantly reduce adipocyte size. Localized hippocampal morphological alterations were observed in OTRF rats. Discussion Caloric restriction was more effective in improving metabolic outcomes, whereas TRF primarily modified behavioral parameters, indicating distinct responses to these dietary interventions.