BRIEF RESEARCH REPORT article
Front. Physiol.
Sec. Metabolic Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1629751
Calorie and Time-Restricted Feeding Improves Liver and Kidney Histopathology in Streptozotocin-Induced Type 1 Diabetic Rats
Provisionally accepted
Indra Putra Taufani1*Sri Rahmatul Laila2Sri Tasminatun1
Sailent Rizki Sari Simaremare3Meity Mardiana3
Jiro Hasegawa Situmorang3*- 1Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia
- 2IPB University, Bogor, Indonesia
- 3National Research and Innovation Agency (BRIN), Bogor, Indonesia
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Type 1 diabetes (T1D) is associated with severe metabolic dysregulation and organ complications such as hepatomegaly and nephropathy. While pharmacological insulin therapy remains the cornerstone of treatment, there is growing interest in dietary interventions that modulate metabolic outcomes independently of insulin. This study aimed to investigate the effects of calorie restriction (CR) combined with time-restricted feeding (TRF) on metabolic and histological parameters in a high-fat diet-fed, streptozotocin-induced rat model of T1D. Male Sprague-Dawley rats were divided into control, diabetic, and two CR-TRF groups (day-fed and night-fed). CR-TRF groups received 70% of the diabetic group's caloric intake during either the light or dark phase. Body weight, fasting glucose, oral glucose tolerance test (OGTT), triglycerides, and water intake were measured. Liver and kidney tissues were evaluated using H&E staining with semi-quantitative histological scoring.Although CR-TRF did not significantly improve body weight, both interventions markedly reduced water intake and improved hepatomegaly. OGTT results showed improved slight glycemic responses in CR-TRF groups, particularly in the day-fed group. Diabetic rats exhibited hepatomegaly and renal tubular damage, which were significantly attenuated by CR-TRF. Histological analysis revealed preserved tissue architecture and reduced vacuolation in both liver and kidney under CR-TRF conditions. CR-TRF significantly improve metabolic and histological outcomes in non-insulin-treated T1D rats. These findings support the potential of circadian-aligned dietary strategies as adjunct therapies for T1D and warrant further exploration in translational models.
Keywords: type 1 diabetes, calorie restriction, time-restricted feeding, metabolic dysfunction, Circadian Rhythm, Hepatomegaly, diabetic nephropathy, glucose tolerance
Received: 16 May 2025; Accepted: 15 Jul 2025.
Copyright: © 2025 Taufani, Laila, Tasminatun, Simaremare, Mardiana and Situmorang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Indra Putra Taufani, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia
Jiro Hasegawa Situmorang, National Research and Innovation Agency (BRIN), Bogor, Indonesia
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