ArticleJournal of biochemical and molecular toxicology2026
Sex-Specific Anti-Inflammatory Effects of Alternate Day Fasting via TLR4 and Leptin Signaling in Middle-Aged Rats.
Article in Journal of biochemical and molecular toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Alternate-day fasting (ADF) may exert age-related anti-inflammatory effects by modulating key metabolic and immune pathways. This study aimed to investigate the sex-specific effects of ADF on inflammation in middle-aged male and female rats and focused on the Toll-like receptor 4 (TLR4) and leptin signaling pathways. A total of 32 rats (16 males, 16 females; 14 months old) were assigned to four groups (n = 8): ad libitum-fed and ADF groups for each sex. The ADF protocol consisted of 24-h fasting every other day for 2 months. Serum and hypothalamic samples were analyzed via ELISA to measure triglyceride, total cholesterol, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), suppressor of cytokine signaling 3 (SOCS3), leptin, and ObRb levels. TLR4 gene expression in the brain and liver was assessed via qRT-PCR. Two months of ADF significantly reduced body weight and retroperitoneal fat mass compared with those of the control groups (p < 0.001). Cumulative food intake and fasting glucose levels decreased in both sexes following ADF (p < 0.001), and serum triglyceride, total cholesterol, TNF-α, and IL-6 levels (p < 0.001) were significantly reduced. Hypothalamic SOCS3 and leptin levels decreased, whereas ObRb expression increased (p < 0.05). Additionally, TLR4 gene expression was significantly downregulated in both tissues (p < 0.001). These findings suggest that ADF is associated with reduced age-related inflammation and alterations in the TLR4 and leptin signaling pathways. The observed downregulation of SOCS3 and upregulation of ObRb indicate enhanced leptin sensitivity, highlighting ADF as a promising strategy to counteract sex-specific aging-related inflammation and leptin resistance.
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