Gender-specific effects of alternate-day fasting on body weight, oxidative stress, and metabolic health in middle-aged rats

Yıl 2025, Cilt: 18 Sayı: 1, 6 - 6

Özgen Kılıç Erkek Gülşah Gündoğdu

https://doi.org/10.31362/patd.1487708

Öz

Purpose: The purpose of this study was to assess the effect of alternate-day fasting (ADF) concerning sex as well as its function in systemic and tissue-level oxidative stress alterations associated with aging.
Materials and methods: Forty-two female (n=21) and male (n=21) Wistar rats (aged 16 months) were separated into six groups (n=7 each): Group-1 (control-male), Group-2 (1-month, ADF-male), Group-3 (2-month, ADF-male), Group-4 (control-female), Group-5 (1-month, ADF-female), and Group-6 (2-month, ADF-female). The ADF protocol was applied every other day for 24-h of fasting (three days/week). Serum samples were analyzed via ELISA to measure total oxidant-antioxidant status (TOS-TAS), and the oxidative stress index (OSI) was calculated.
Results: 2-months of ADF treatment reduced body weight (BW) compared compliance control groups (p<0.001). All groups' cumulative food intake and retroperitoneal fat weight decreased with ADF (p<0.05). Both 1-month and 2-month ADF interventions had positive effects on reducing TOS and OSI in both liver and serum, with a significant decrease observed in both groups compared to their respective controls (p<0.001). The liver TAS level significantly increased in female rats (p<0.05), but this increase did not reach a significant level in male rats. The difference in the serum TAS level between the groups was not significant.
Conclusions: This study evaluated the effects of ADF on BW, food consumption, and oxidative stress parameters in male and female rats. The findings highlight ADF's potential benefits in weight management and reducing oxidative stress. This study represents an important step in understanding the effects of ADF on metabolic health and in identifying potential clinical applications.

Anahtar Kelimeler

Aging, alternate-day fasting, food intake, gender, oxidative stress

Etik Beyan

Animal Experiments were approved by the Medical Ethics Committee of Pamukkale University (dated 15.12.2023 and numbered PAUHADYEK-2023/60758568-020-468703).

Orta yaş sıçanlarda gün aşırı açlık protokolünün vücut ağırlığı, oksidatif stres ve metabolik sağlık üzerine cinsiyete özgü etkileri

Öz

Amaç: Bu çalışmada, gün aşırı açlık protokolünün (ADF) cinsiyete özgü etkileri ve sistemik ve doku düzeyindeki oksidatif stres üzerine etkilerinin yaşlanmaya bağlı olarak değerlendirilmesi amaçlanmıştır.
Gereç ve yöntem: Kırk iki dişi (n=21) ve erkek (n=21) 16 aylık Wistar sıçanları altı gruba (n=7) ayrıldı: Grup-1 (kontrol-erkek), Grup-2 (1 ay, ADF-erkek), Grup-3 (2 ay, ADF-erkek), Grup-4 (kontrol-dişi), Grup-5 (1 ay, ADF-dişi) ve Grup-6 (2 ay, ADF-dişi). ADF protokolü günaşırı 24 saatlik oruç tutma şeklinde uygulandı (haftada üç gün). Serum örnekleri, ELISA yöntemiyle toplam oksidan-antioksidan durumu (TOS-TAS) ölçmek için alındı ve oksidatif stres indeksi (OSI) hesaplandı.
Bulgular: 2 aylık-ADF tedavisinin kümültatif control gruplarıyla karşılaştırıldığında vücut ağırlığında (VA) anlamlı azalma tespit edildi (p<0,001). Tüm gruplarda kümülatif gıda alımı ve retroperitoneal yağ ağırlığı ADF ile azaldığı görüldü (p<0,05). Hem 1 aylık hem de 2 aylık ADF müdahaleleri, hem karaciğer hem de serumda TOS ve OSI'yi azaltmada olumlu etkiler gösterdi ve her iki grup da kendi kontrollerine göre anlamlı bir azalma gösterdi (p<0,001). Karaciğer TAS seviyesi dişi sıçanlarda anlamlı olarak arttı (p<0,05), ancak erkek sıçanlarda bu artış anlamlı bir seviyeye ulaşmadı. Gruplar arasındaki serum TAS seviyesinde anlamlı fark saptanmadı.
Sonuç: Bu çalışma, erkek ve dişi sıçanlarda ADF'nin VA, gıda tüketimi ve oksidatif stres parametreleri üzerindeki etkilerini değerlendirdi. Bulgular, ADF'nin kilo yönetimi ve oksidatif stresi azaltmada potansiyel faydalarını vurgulamaktadır. Sonuç olarak, ADF'nin metabolik sağlık üzerindeki etkilerini anlamada ve olası klinik uygulamaları belirlemede önemli bir adımı temsil etmektedir.

Anahtar Kelimeler

Yaşlanma, alternatif günlerde açlık, gıda alımı, cinsiyet, oksidatif stres

Kaynakça

• 1. López Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013;153:1194-1217. https://doi.org/10.1016%2Fj.cell.2013.05.039
• 2. Çakatay U, Aydin S, Yanar K, Uzun H. Gender-dependent variations in systemic biomarkers of oxidative protein, DNA, and lipid damage in aged rats. Aging Male 2010;13:51-58. https://doi.org/10.3109/13685530903236470
• 3. Maldonado E, Morales Pison S, Urbina F, Solari A. Aging hallmarks and the role of oxidative stress. Antioxidants 2023;12:651. https://doi.org/10.3390/antiox12030651
• 4. Sharifi Rad M, Anil Kumar NV, Zucca P, et al. Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Front Physiology 2020;11:694. https://doi.org/10.3389/fphys.2020.00694
• 5. Schriner SE, Linford NJ, Martin GM, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 2005;308:1909-1911. https://doi.org/10.1126/science.1106653
• 6. Shields HJ, Traa A, Van Raamsdonk JM. Beneficial and detrimental effects of reactive oxygen species on lifespan: a comprehensive review of comparative and experimental studies. Front Cell Dev Biology 2021;9:628157. https://doi.org/10.3389/fcell.2021.628157
• 7. Navarro A, Boveris A. Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. Am J Physiol Regul Integr Comp Physiol 2004;287:1244-1249. https://doi.org/10.1152/ajpregu.00226.2004
• 8. Luceri C, Bigagli E, Femia AP, Caderni G, Giovannelli L, Lodovici M. Aging related changes in circulating reactive oxygen species (ROS) and protein carbonyls are indicative of liver oxidative injury. Toxicology Reports 2018;5:141-145. https://doi.org/10.1016/j.toxrep.2017.12.017
• 9. Lebel M, de Souza Pinto NC, Bohr VA. Metabolism, genomics, and DNA repair in the mouse aging liver. Current gerontology and geriatrics research 2011;2011:859415. https://doi.org/10.1155%2F2011%2F859415
• 10. Soares NL, Dorand VAM, Cavalcante HC, et al. Does intermittent fasting associated with aerobic training influence parameters related to the gut-brain axis of Wistar rats? Journal of Affective Disorders 2021;293:176-185. https://doi.org/10.1016/j.jad.2021.06.028
• 11. Badreh F, Joukar S, Badavi M, Rashno M, Dehesh T. The effects of age and fasting models on blood pressure, insulin/glucose profile, and expression of longevity proteins in male rats. Rejuvenation Research 2020;23:224-236. https://doi.org/10.1089/rej.2019.2205
• 12. Carvajal V, Marín A, Gihardo D, Maluenda F, Carrasco F, Chamorro R. Intermittent fasting and human metabolic health. Rev Med Chile 2023;151:81-100. https://doi.org/10.4067/s0034-98872023000100081
• 13. Gabel K, Hoddy KK, Haggerty N, et al. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: a pilot study. Nutrition and Healthy Aging 2018;4:345-353. https://doi.org/10.3233/nha-170036
• 14. Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Research Reviews 2017;39:46-58. https://doi.org/10.1016/j.arr.2016.10.005
• 15. Harris L, Hamilton S, Azevedo LB, et al. Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Evidence Synthesis 2018;16:507-547. https://doi.org/10.11124/jbisrir-2016-003248
• 16. Park J, Seo YG, Paek YJ, Song HJ, Park KH, Noh HM. Effect of alternate-day fasting on obesity and cardiometabolic risk: a systematic review and meta-analysis. Metabolism 2020;111:154336. https://doi.org/10.1016/j.metabol.2020.154336
• 17. Moon S, Kang J, Kim SH, et al. Beneficial effects of time-restricted eating on metabolic diseases: a systemic review and meta-analysis. Nutrients 2020;12:1267. https://doi.org/10.3390/nu12051267
• 18. Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutrition Reviews 2015;73:661-674. https://doi.org/10.1093/nutrit/nuv041
• 19. Lee JH, Verma N, Thakkar N, Yeung C, Sung HK. Intermittent fasting: physiological implications on outcomes in mice and men. Physiology 2020;35:185-195. https://doi.org/10.1152/physiol.00030.2019
• 20. Catterson JH, Khericha M, Dyson MC, et al. Short-term, intermittent fasting induces long-lasting gut health and TOR-independent lifespan extension. Current Biology 2018;28:1714-1724. https://doi.org/10.1016/j.cub.2018.04.015
• 21. Vassalle C, Novembrino C, Maffei S, et al. Determinants of oxidative stress related to gender: relevance of age and smoking habit. Clin Chem Lab Med 2011;49:1509-1513. https://doi.org/10.1515/CCLM.2011.622
• 22. Takahashi M, Miyashita M, Park JH, et al. The association between physical activity and sex-specific oxidative stress in older adults. J Sports Sci Med 2013;12:571-578. 23. Bilibio BLE, Dos Reis WR, Compagnon L, et al. Effects of alternate-day fasting and time-restricted feeding in obese middle-aged female rats. Nutrition 2023;116:112198. https://doi.org/10.1016/j.nut.2023.112198
• 24. Munhoz AC, Vilas Boas EA, Panveloski Costa AC, et al. Intermittent fasting for twelve weeks leads to increases in fat mass and hyperinsulinemia in young female Wistar rats. Nutrients 2020;12:1029. https://doi.org/10.3390/nu12041029
• 25. Olsen MK, Choi MH, Kulseng B, Zhao CM, Chen D. Time-restricted feeding on weekdays restricts weight gain: a study using rat models of high-fat diet-induced obesity. Physiology Behavior 2017;173:298-304. https://doi.org/10.1016/j.physbeh.2017.02.032
• 26. Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry 2005;38:1103-1011. https://doi.org/10.1016/j.clinbiochem.2005.08.008
• 27. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical Biochemistry 2004;37:277-285. https://doi.org/10.1016/j.clinbiochem.2003.11.015
• 28. Mattson MP, Allison DB, Fontana L, et al. Meal frequency and timing in health and disease. PNAS 2014;111:16647-16653. https://doi.org/10.1073/pnas.1413965111
• 29. Baumeier C, Kaiser D, Heeren J, et al. Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2015;1851:566-576. https://doi.org/10.1016/j.bbalip.2015.01.013
• 30. Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O. Timed high‐fat diet resets circadian metabolism and prevents obesity. FASEB J 2012;26:3493-3502. https://doi.org/10.1096/fj.12-208868
• 31. Cottone P, Sabino V, Steardo L, Zorrilla EP. Consummatory, anxiety-related and metabolic adaptations in female rats with alternating access to preferred food. Psychoneuroendocrinology 2009;34:38-49. https://doi.org/10.1016/j.psyneuen.2008.08.010
• 32. Wang L, Suyama S, Lee SA, et al. Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain. Front Nutr 2022;9:994827. https://doi.org/10.3389/fnut.2022.994827
• 33. Park S, Yoo KM, Hyun JS, Kang S. Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets. The Journal of Nutritional Biochemistry 2017;40:14-22. https://doi.org/10.1016/j.jnutbio.2016.10.003
• 34. Carpentier AC. 100th anniversary of the discovery of insulin perspective: insulin and adipose tissue fatty acid metabolism. Am J Physiol Endocrinol Metab 2021;320:653-670. https://doi.org/10.1152/ajpendo.00620.2020
• 35. Stockman MC, Thomas D, Burke J, Apovian CM. Intermittent fasting: is the wait worth the weight? Curr Obes Rep 2018;7:172-185. https://doi.org/10.1007/s13679-018-0308-9
• 36. Varady KA, Hudak CS, Hellerstein MK. Modified alternate-day fasting and cardioprotection: relation to adipose tissue dynamics and dietary fat intake. Metabolism 2009;58:803-811. https://doi.org/10.1016/j.metabol.2009.01.018
• 37. Kayali R, Çakatay U, Tekeli F. Male rats exhibit higher oxidative protein damage than females of the same chronological age. Mechanisms of Ageing and Development 2007;128:365-369. https://doi.org/10.1016/j.mad.2007.03.003
• 38. Höhn A, König J, Grune T. Protein oxidation in aging and the removal of oxidized proteins. Journal of Proteomics 2013;92:132-159. https://doi.org/10.1016/j.jprot.2013.01.004
• 39. Pandey KB, Mehdi MM, Maurya PK, Rizvi SI. Plasma protein oxidation and its correlation with antioxidant potential during human aging. Disease Markers 2010;29:31-36. https://doi.org/10.3233/dma-2010-0723
• 40. Marczuk Krynickaabcdef D, Hryniewieckibe T, Piątekbf J, Paluszak J. The effect of brief food withdrawal on the level of free radicals and other parameters of oxidative status in the liver. Med Sci Monit 2003;9:131-135.
• 41. Sorensen M, Sanz A, Gomez J, et al. Effects of fasting on oxidative stress in rat liver mitochondria. Free Radical Research 2006;40:339-347. https://doi.org/10.1080/10715760500250182
• 42. Bhutani S, Klempel MC, Berger RA, Varady KA. Improvements in coronary heart disease risk indicators by alternate‐day fasting involve adipose tissue modulations. Obesity 2010;18:2152-2159. https://doi.org/10.1038/oby.2010.54
• 43. Descamps O, Riondel J, Ducros V, Roussel AM. Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting. Mechanisms of Ageing and Development 2005;126:1185-1191. https://doi.org/10.1016/j.mad.2005.06.007
• 44. Le Bourg E. Hormesis, aging and longevity. Biochimica et Biophysica Acta (BBA)-General Subjects 2009;1790:1030-1039. https://doi.org/10.1016/j.bbagen.2009.01.004