The potential intervention of time-restricted feeding for modulating hepatic gene expression of the inflammatory mediators and serum adipokine balance in high-fat diet-induced steatosis.

Abstract

Time-restricted feeding (TRF), a chrono-nutrition-based intervention, has shown promise in mitigating the adverse effects of high-fat diets (HFDs) on metabolic and hepatic health. This study evaluates the protective effects of TRF on hepatic gene expression, inflammatory markers, and serum adipocytokine levels in a rat model of HFD-induced hepatic steatosis. Forty male Wistar rats were divided into four groups: control, control + TRF, HFD, and HFD+TRF. The TRF was implemented as an 18-hour fasting period followed by a 6-hour feeding window for 12 weeks. Body composition, glucose homeostasis, lipid profiles, serum inflammatory markers, and adipocytokines (adiponectin, leptin, resistin) were measured. Hepatic oxidative stress markers (malodialdehyde, total antioxidant capacity) and gene expression of inflammatory mediators (nuclear factor-κB, tumor necrosis factor-α, interleukin-1β, interleukin-6, high-sensivity-C-reactive protein) were assessed. Histopathological analysis of liver tissue evaluated steatosis and p53 expression. TRF significantly reduced body weight in HFD-fed rats from 396.5±6.9 g to 350±6.4 g (p<0.0001). Homeostasis model assessment of insulin resistance (HOMA-IR) decreased from 2.03±0.06 to 0.72±0.05 (p<0.05), and hepatic malodialdehyde levels were reduced from 25 to 12.42 nmol/g (p<0.0001). TRF also downregulated inflammatory cytokines, including tumor necrosis factor-a and nuclear factor-κB, while increasing adiponectin levels and improving adiponectin/leptin and adiponectin/resistin ratios. Histological examination showed steatosis improved from grade 3 to grade 1 or 0. We found that RF effectively mitigates HFD-induced hepatic steatosis and metabolic dysfunction by reducing oxidative stress and inflammation and modulating adipocytokine balance. These findings highlight TRF's potential as a therapeutic strategy for managing hepatic and metabolic disorders.