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

Abstract

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.

Keywords

• Osteoarthritis
• Alternate-day fasting
• Leptin
• Inflammation
• Aging

Alternatif Günlerde Açlık Serum Leptin ve SOCS3 Düzeylerini Düzenler ve Osteoartritli Erişkin Sıçan Modelinde İnflamasyonu Azaltır

Öz

Amaç: Bu çalışma, farmakolojik olmayan bir müdahale olan alternatif günlerde açlık (ADF), deneysel diz osteoartriti (OA) oluşturulmuş erişkin sıçanlarda inflamasyon, oksidatif stres ve lipid metabolizması üzerindeki etkilerini araştırmayı amaçlandıÇalışmada özellikle serum leptin ve SOCS3 düzeyleri ile kıkırdak histopatolojisine odaklanıldı. Yöntemler: Yirmi dört erkek Wistar sıçanı (16 haftalık) rastgele dört gruba ayrıldı: Kontrol (K), OA, ADF ve OA+ADF. OA modeli, intraartiküler monosodyum iyodoasetat (MIA) enjeksiyonu ile oluşturuldu. ADF uygulaması 28 gün boyunca (24 saat açlık/beslenme döngüleri) gerçekleştirildi. Biyokimyasal analizlerde açlık kan şekeri (AKŞ), lipid profili, leptin, SOCS3, tümör nekroz faktörü-alfa (TNF-α), interlökin-6 (IL-6) ve total oksidan–antioksidan durumu (TOS-TAS) değerlendirildi. Histopatolojik inceleme hematoksilen&eozin ve Masson trikrom boyamaları ile yapıldı. Bulgular: Kontrol grubu ile karşılaştırıldığında, OA grubunda vücut ağırlığı (VA), AKŞ, leptin, IL-6, TNF-α ve TOS düzeyleri artarken; TAS ve SOCS3 düzeyleri azaldı (p<0.05). ADF grubunda kontrol grubuna kıyasla olumsuz metabolik etki gözlenmedi; glukoz ve sitokin düzeyleri normal sınırlar içinde kaldı. Özellikle OA+ADF grubunda VA, AKŞ, leptin, IL-6, TNF-α ve TOS düzeyleri anlamlı olarak daha düşük; TAS ve SOCS3 düzeyleri ise daha yüksek bulundu (p<0.05). Histolojik olarak OA+ADF grubu, OA grubuna kıyasla daha iyi kıkırdak korunumu ve daha az dejeneratif değişiklik gösterdi. Ayrıca ADF uygulaması gastroknemius kas ağırlığını düzenledi ve metabolik parametreleri iyileştirdi. Sonuç: ADF, deneysel OA’da sistemik inflamasyonu azaltarak, leptin-SOCS3 sinyal yolunu düzenleyerek ve oksidatif stresi hafifleterek koruyucu etki göstermektedir. Bulgular, ADF’nin yaşlanma sürecinde OA progresyonunu modüle etmede umut verici bir beslenme stratejisi olabileceğini düşündürmektedir.

Anahtar Kelimeler

• Osteoartrit
• Alternatif günlerde açlık
• Leptin
• İnflamasyon
• Yaşlanma

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