Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2023-01-01 Epub Date: 2023-11-28 DOI:10.5603/fhc.95905
Sara Adel Hosny, Mohammed Hafez Ahmed Moustafa, Fatma Mahmoud Mehina, Marwa Mohamed Sabry
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Abstract

Introduction: High-fructose, high-fat diet consumption (HFHF) is one of the primary causes of non-alcoholic fatt liver disease (NAFLD), which is due to impaired beta-oxidation or apolipoprotein secretion by hepatocytes. Activation of autophagy in hepatocytes could be a therapeutic method against hepatic complications. This study was designed to compare effects of rapamycin and intermittent fasting-inducing autophagy in rats with experimentally induced nonalcoholic fatty liver.

Material and methods: Male rats were divided into five groups: C (control, n = 6), the experimental group (EX) subdivided, EXIa (HFHF, n = 6), EXIb (recovery, n = 6), EXII (rapamycin, n = 6) and EXIII (intermittent fasting, n = 6). All rats in the experimental group received HFHF diet for 8 weeks to induce nonalcoholic-fatty liver and obesity. Then, for the next 8 weeks the animals received either a daily oral dose of rapamycin (EXII group) or to intermittent fasting (IF) for 16 hours daily (EXIII group). Blood samples were drawn, and serum TG concentration as well as ALT and AST activities were determined. Hepatic sections were examined by light and electron microscopy. LC3B immunohistochemical staining, morphometric and statistical studies were performed.

Results: Subgroups EXIa (HFHF subgroup) and EXIb (Recovery subgroup) showed marked increase in TG, ALT, and AST levels associated with loss of normal hepatic architecture, cytoplasmic vacuolations and faint LC3B immunoreactivity. Ultrathin sections exhibited many autophagosomes in hepatocytes. On the other hand, rapamycin (EXII) and IF (EXIII) groups showed significant improvement to a variable extent in comparison to EXI groups.

Conclusions: It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes.

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雷帕霉素诱导自噬与间歇性禁食对脂肪肝动物模型的治疗作用。
导读:高果糖、高脂肪饮食(HFHF)是导致非酒精性脂肪性肝病(NAFLD)的主要原因之一,这是由于肝细胞β -氧化或载脂蛋白分泌受损。激活肝细胞自噬可能是治疗肝脏并发症的一种方法。本研究旨在比较雷帕霉素和间歇性禁食诱导的自噬对实验性非酒精性脂肪肝大鼠的影响。材料与方法:将雄性大鼠分为5组:C组(对照组,n = 6),实验组(EX)再分组,EXIa组(HFHF, n = 6), EXIb组(恢复组,n = 6), EXII组(雷帕霉素,n = 6), EXIII组(间歇性禁食组,n = 6)。实验组大鼠连续8周采用HFHF饮食诱导非酒精性脂肪肝和肥胖。然后,在接下来的8周内,这些动物要么每天口服雷帕霉素(EXII组),要么每天间歇性禁食(IF) 16小时(EXIII组)。取血,测定血清TG浓度及ALT、AST活性。肝脏切片行光镜和电镜检查。LC3B免疫组织化学染色、形态计量学和统计学研究。结果:EXIa亚组(hhff亚组)和EXIb亚组(恢复亚组)显示TG, ALT和AST水平显著升高,与正常肝脏结构丧失,细胞质空泡化和LC3B免疫反应性减弱相关。肝细胞超薄切片显示有许多自噬体。另一方面,雷帕霉素(EXII)和IF (EXIII)与EXI相比有不同程度的显著改善。结论:雷帕霉素联合间歇性禁食可通过诱导肝细胞自噬,显著改善nafld诱导的肝脏结构和功能改变。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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