Metformin and intermittent fasting mitigate high fat-fructose diet-induced liver and skeletal muscle injury through upregulation of mitophagy genes in rats

IF 2.5 Q2 MULTIDISCIPLINARY SCIENCES

Beni-Suef University Journal of Basic and Applied Sciences Pub Date : 2024-09-06 DOI:10.1186/s43088-024-00548-z

Nermeen Bastawy, Ghada Farouk Soliman, Nermeen Bakr Sadek, Doaa Mostafa Gharib, Mai Abdelaziz Gouda, Laila Ahmed Rashed, Hanan Abdallah, Dina Hisham, Omnia Mohamed Abdel-Maksoud

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Abstract

Background

High fat-fructose diet is a proinflammatory diet that increases risk of hepatocytes and myocytes steatosis and fibrosis. Finding anti-inflammatory strategies to fight these harmful effects is paid attention to nowadays. This study compared the effects of two widely anti-inflammatory interventions—metformin and intermittent fasting on myocytes and hepatocyte injury induced by proinflammatory diet and tracking possible underlying mechanisms. In this work, rats fed high fat-fructose diet were subdivided into untreated group, treated by metformin, and/or intermittent fasting.

Results

Metformin (300 mg/kg/day) and intermittent fasting (3 days/week) specially their combination for 4 weeks showed significant improvement in insulin resistance, lipid profile, antioxidants (p < 0.05), as well as enhanced hepatocytes and myocytes repair and reduced collagen deposition through upregulation of mitophagy-related genes: PINK1, PARKIN, LAMP2, and PPAR-α (p < 0.05).

Conclusions

Intermittent fasting has beneficial metabolic and molecular therapeutic effects against proinflammatory diet-induced injury. Their results are like those of metformin sparing its adverse effects. Their combination showed additional effects against diet-induced myocytes and hepatocyte injury by upregulation of mitophagy-related genes without the need of increasing the dose of metformin.

Graphic abstract

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二甲双胍和间歇性禁食通过上调有丝分裂基因减轻高脂果糖饮食对大鼠肝脏和骨骼肌的损伤

背景高脂果糖饮食是一种促炎饮食，会增加肝细胞和肌细胞脂肪变性和纤维化的风险。如今，寻找抗炎策略来对抗这些有害影响已受到重视。这项研究比较了两种广泛的抗炎干预措施--二甲双胍和间歇性禁食--对原炎症饮食诱导的肌细胞和肝细胞损伤的影响，并追踪可能的潜在机制。结果二甲双胍（300 毫克/千克/天）和间歇性禁食（3 天/周）（特别是它们的组合）在 4 周内显著改善了胰岛素抵抗、血脂、抗氧化剂（p < 0.05），并通过上调有丝分裂相关基因增强了肝细胞和肌细胞的修复能力，减少了胶原沉积：结论间歇性禁食对前炎饮食诱导的损伤具有有益的代谢和分子治疗作用。其结果与二甲双胍相似，但二甲双胍的不良反应较少。它们的组合通过上调有丝分裂相关基因对饮食诱导的肌细胞和肝细胞损伤有额外的作用，而无需增加二甲双胍的剂量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Beni-Suef University Journal of Basic and Applied Sciences MULTIDISCIPLINARY SCIENCES-

CiteScore

2.60

自引率

0.00%

发文量

期刊介绍： Beni-Suef University Journal of Basic and Applied Sciences (BJBAS) is a peer-reviewed, open-access journal. This journal welcomes submissions of original research, literature reviews, and editorials in its respected fields of fundamental science, applied science (with a particular focus on the fields of applied nanotechnology and biotechnology), medical sciences, pharmaceutical sciences, and engineering. The multidisciplinary aspects of the journal encourage global collaboration between researchers in multiple fields and provide cross-disciplinary dissemination of findings.

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