Alternate-Day Fasting Modulates Serum Leptin and SOCS3 Levels and Attenuates Inflammation in an Adult Rat Model of Osteoarthritis

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Objective: This study investigated the effects of alternate-day fasting (ADF), a nonpharmacological intervention, on inflammation, oxidative stress, and lipid metabolism in adult rats with experimental knee osteoarthritis (KOA), with a particular emphasis on serum leptin and SOCS3 levels, as well as cartilage histopathology. Methods: Twenty-four male Wistar rats (16-weeks old) were randomly assigned to four groups: C (control), OA, ADF, and OA+ADF. The KOA model was induced by intra-articular monosodium iodoacetate (MIA) injection. ADF was applied for 28 days (24-hour fasting/feeding cycles). Biochemical analyses included fasting blood glucose(FBG), lipid profile, leptin, SOCS3, tumor necrosis factor-alpha(TNF-α), interleukin-6 (IL-6), and total oxidant-antioxidant status (TOS-TAS) analyses. Histopathological evaluation was performed via hematoxylin&eosin and Masson’s trichrome staining. Results: Compared with the C group, the OA group presented increased body weight (BW), FBG, leptin, IL-6, TNF-α, and TOS and decreased TAS and SOCS3 levels (p<0.05). Compared with the C group, the ADF group presented no adverse metabolic effects and maintained normal glucose and cytokine levels. Notably, the OA+ADF group demonstrated significantly lower BW, FBG, leptin, IL-6, TNF-α, and TOS levels and significantly greater TAS and SOCS3 levels than the OA group did (p<0.05). Histologically, the OA+ADF group presented better cartilage preservation and fewer degenerative changes than did the OA group. Additionally, ADF modulated gastrocnemius muscle weight and improved metabolic parameters. Conclusion: ADF exerts protective effects in experimental OA by reducing systemic inflammation, regulating leptin-SOCS3 signaling, and mitigating oxidative stress. These findings suggest that ADF is a promising dietary strategy for modulating OA progression during aging.