Time-restricted feeding during the inactive phase vs. ad libitum feeding: diet-dependent effects on weight and metabolic markers in male Wistar rats

Background/objectives In recent years, intermittent fasting has become a popular method for preventing and treating obesity and chronic diseases. This study explored the metabolic and inflammatory effects of inactive-phase (Day) time-restricted feeding (TRF) vs. ad libitum feeding (Ad) in rats under high-fat (HF) and standard (S) diet for 8 weeks. Methods Four groups (TRF + HF, TRF + S, Ad + S, Ad + HF; n = 7 each) were monitored for temporal changes in key biomarkers, including TNF-α, IL-6, LPS, insulin, glucose, and lipid profiles, and body weight. Baseline-adjusted two-way ANCOVA was used to evaluate the main effects of Diet and Feeding pattern and their interaction, with complementary multivariate analyses performed as sensitivity analyses. Results Body weight was significantly associated with both Diet and Feeding pattern after baseline adjustment, with the greatest observed weight gain in Ad + HF and the smallest in TRF + S. TNF-α showed a significant Diet × Feeding interaction, characterized by marked reductions in both TRF groups and little change in Ad + HF. Lipid metabolism exhibited distinct interactions between diet type and feeding regimens. Total cholesterol levels increased in both ad libitum -fed groups, whereas a reduction was observed in the TRF + S group. Triglyceride responses also showed pronounced treatment effects, with the TRF + HF group demonstrating the greatest decrease over the intervention period. IL-6, LPS, insulin, glucose, and LDL-C did not display significant group × time interactions. Conclusions Overall, inactive-phase time-restricted feeding was associated with lower weight gain, favorable changes in selected lipid parameters, and a reduction in TNF-α. No significant Diet × Feeding interactions were observed for IL-6 or LPS, indicating that the inflammatory findings were specific to TNF-α rather than reflective of a generalized anti-inflammatory effect. However, because food intake was not quantitatively measured, these differences cannot be attributed to meal timing independently of possible differences in total energy intake.