Alternatif günlerde açlık yüksek fruktoz kaynaklı TGF-beta/Smad sinyal yolağının aktivasyonunu azaltır

Year 2025, Volume: 18 Issue: 1, 16 - 16

Gülşah Gündoğdu , Özgen Kılıç Erkek , Ezgi Duman

https://doi.org/10.31362/patd.1583603

Abstract

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 faktörü-beta1 (TGF-β1) / decapentaplegic homolog 2'ye karşı ana protein (Smad2) sinyal yolunun modülasyonuna odaklanmaktadır.
Gereç ve yöntem: Sıçanlar dört grupta (her grup için n=7) çalışmaya dahil edilmiştir: Kontrol, ADF, HF (içme suyunda %20 fruktoz), ve HF+ADF. ADF protokolü, 5 hafta boyunca 24 saat serbest yem tüketimi ve onu takiben 24 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 (TOS-TAS) düzeyleri ELISA yöntemi ile analiz edilmiştir.
Bulgular: Sonuçlar, HF'nin final BW'yi anlamlı derecede artırdığını ve ADF'nin bu kilo alımını azalttığını göstermiştir (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). Ayrıca, ADF, serum TGF-β1, Smad2 ve CTGF seviyelerini düşürerek TGF-β1/Smad2 yolunun aktivasyonunu önemli ölçüde azaltmış (p<0,05) ve fruktoz kaynaklı metabolik düzensizliklere karşı koruyucu bir role işaret etmektedir.
Sonuç: Elde edilen veriler ADF'nin, özellikle oksidatif stres ve TGF-β1/Smad2 yolağını düzenleyerek, aşırı fruktoz alımı ile gerçekleşen metabolik etkileri hafifletmek için etkili bir diyet müdahalesi olabileceğini düşündürmektedir.

Keywords

Alternatif günlerde açlık, yüksek fruktoz, TGF-β1/Smad2 yolağı

Alternative day fasting protocol Attenuates high fructose-induced activation of the TGF-beta/Smad signaling pathway

Abstract

Purpose: This study aims to explore the protective effects of alternate-day fasting (ADF) against metabolic disturbances induced by high fructose (HF) intake, with a particular focus on modulating the transforming growth factor-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% fructose in drinking water), and HF+ADF. The ADF protocol was applied with 24 hours of ad libitum feeding followed by 24 hours of fasting over a 5-week period. After five weeks, body weight (BW), muscle, and fat mass were measured. Serum samples were analyzed using ELISA to assess levels of TGF-β1, Smad2, connective tissue growth 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), but mitigated fructose-induced retroperitoneal fat accumulation. TAS levels were higher, and TOS levels were lower in 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 a protective role against fructose-induced metabolic dysregulation.
Conclusions: These findings suggest that ADF could be an effective dietary intervention for mitigating the metabolic impact of excessive fructose intake, particularly by regulating oxidative stress and the TGF-β1/Smad2 pathway.

Keywords

Alternate-day fasting, high-fructose, TGF-β1/Smad2 pathway

Ethical Statement

Ethics Committee approval, dated 27 June 2024 and numbered PAUHADYEK-2024/60758568-020-544586 was received from the Local Ethics Council of Animal Experiments, Pamukkale University.

Supporting Institution

Pamukkale University

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