TY - JOUR T1 - Alternative day fasting protocol attenuates high fructose-induced activation of the TGF-beta/Smad signaling pathway TT - Alternatif günlerde açlık yüksek fruktoz kaynaklı TGF-beta/Smad sinyal yolağının aktivasyonunu azaltır AU - Kılıç Erkek, Özgen AU - Gündoğdu, Gülşah AU - Duman, Ezgi PY - 2025 DA - January Y2 - 2024 DO - 10.31362/patd.1583603 JF - Pamukkale Medical Journal JO - Pam Med J PB - Pamukkale University WT - DergiPark SN - 1308-0865 SP - 167 EP - 178 VL - 18 IS - 1 LA - en AB - Purpose: This study aims to explore the protective effects of alternate-day fasting (ADF) against metabolicdisturbances induced by high fructose (HF) intake, with a particular focus on modulating the transforming growthfactor-beta1 (TGF-β1) / mother against decapentaplegic homolog 2 (Smad2) signaling pathway.Materials and methods: Four groups of rats (n=7 per group) were included: Control, ADF, HF (20% fructosein drinking water), and HF+ADF. The ADF protocol was applied with 24 hours of ad libitum feeding followedby 24 hours of fasting over a 5-week period. After five weeks, body weight (BW), muscle, and fat mass weremeasured. Serum samples were analyzed using ELISA to assess levels of TGF-β1, Smad2, connective tissuegrowth factor (CTGF), and total oxidant-antioxidant status (TOS-TAS).Results: Results indicated that that HF significantly increased final BW, and ADF reduced this weight gain(p=0.001). ADF also led to lower gastrocnemius-soleus muscle weights compared to controls (p=0.001), butmitigated fructose-induced retroperitoneal fat accumulation. TAS levels were higher, and TOS levels were lowerin the ADF groups, showing an antioxidant shift (p<0.05). Moreover, ADF significantly attenuated the TGF-β1/Smad2 pathway activation by decreasing serum TGF-β1, Smad2, and CTGF levels (p<0.05), suggesting aprotective role against fructose-induced metabolic dysregulation.Conclusions: These findings suggest that ADF could be an effective dietary intervention for mitigating themetabolic impact of excessive fructose intake, particularly by regulating oxidative stress and the TGF-β1/Smad2pathway. KW - Alternate-day fasting KW - high-fructose KW - TGF-β1/Smad2 pathway KW - oxidative stress KW - metabolic health N2 - Amaç: Bu çalışma, yüksek fruktoz (HF) alımının yol açtığı metabolik bozukluklara karşı alternatif gün orucu(ADF) uygulamasının koruyucu etkilerini incelemeyi amaçlamakta olup, özellikle transformasyon büyüme faktörübeta1(TGF-β1) / decapentaplegic homolog 2'ye karşı ana protein (Smad2) sinyal yolunun modülasyonunaodaklanmaktadır.Gereç ve yöntem: Sıçanlar dört grupta (her grup için n=7) çalışmaya dahil edilmiştir: Kontrol, ADF, HF (içmesuyunda %20 fruktoz), ve HF+ADF. ADF protokolü, 5 hafta boyunca 24 saat serbest yem tüketimi ve onu takiben24 saat açlık olarak gerçekleştirilmiştir. Beş hafta sonunda vücut ağırlığı (VA), kas ve yağ kütlesi ölçülmüştür.Serum örneklerinde TGF-β1, Smad2, bağ dokusu büyüme faktörü (CTGF) ve total oksidan-antioksidan (TOSTAS)düzeyleri ELISA yöntemi ile analiz edilmiştir.Bulgular: Sonuçlar, HF'nin final BW'yi anlamlı derecede artırdığını ve ADF'nin bu kilo alımını azalttığınıgöstermiştir (p=0,001). ADF, kontrol grubuna kıyasla gastrocnemius-soleus kas ağırlıklarını azaltmış (p=0,001),ancak fruktoz kaynaklı retroperitoneal yağ birikimini hafifletmiştir. ADF gruplarında TAS düzeyleri daha yüksek,TOS düzeyleri ise daha düşük bulunmuş olup, bu da bir antioksidan kaymasına işaret etmiştir (p<0,05). 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