高胆固醇斑马鱼饮食可促进高胆固醇血症和空腹相关性肝脏脂肪变性。

IF 5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Journal of Lipid Research Pub Date : 2024-10-01 Epub Date: 2024-08-31 DOI:10.1016/j.jlr.2024.100637
Yang Jin, Darby Kozan, Eric D Young, Monica R Hensley, Meng-Chieh Shen, Jia Wen, Tabea Moll, Jennifer L Anderson, Hannah Kozan, John F Rawls, Steven A Farber
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引用次数: 0

摘要

斑马鱼是研究脂质代谢和阐明人类脂质相关疾病分子基础的理想模式生物。小鼠模型有各种标准化的高脂饮食,如高胆固醇饮食(HCD),而斑马鱼则不同,目前还没有统一的斑马鱼高脂饮食方案。在本研究中,我们开发了一种改进的 HCD 方案,并以剂量和时间依赖的方式全面测试了其对斑马鱼脂质沉积和脂蛋白调节的影响。同时还验证了日粮的稳定性、可重复性和鱼的适口性。喂食 HCD 的斑马鱼出现了高胆固醇血症,表现为含载脂蛋白 B 的脂蛋白(载脂蛋白 B-LP)显著升高,血浆中胆固醇和胆固醇酯水平升高。给幼鱼喂食 HCD 8 天会产生肝脏脂肪变性,禁食 1 天后变得更加稳定和严重,并伴有不透明肝脏表型(透射光下呈深色)。与幼鱼不同,成鱼喂食 HCD 14 天后禁食 3 天,虽然血浆中载脂蛋白 B-LP 水平较高,脂肪组织中的脂肪生成基因 fasn 上调,但并未出现稳定的脂肪肝表型。总之,我们的 HCD 斑马鱼方案是研究高水平膳食胆固醇的生理和生化反应的时间特征的一种有效而可靠的方法,并为了解脂肪肝的发病机制提供了启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver steatosis.

Zebrafish are an ideal model organism to study lipid metabolism and to elucidate the molecular underpinnings of human lipid-associated disorders. Unlike murine models, to which various standardized high lipid diets such as a high-cholesterol diet (HCD) are available, there has yet to be a uniformly adopted zebrafish HCD protocol. In this study, we have developed an improved HCD protocol and thoroughly tested its impact on zebrafish lipid deposition and lipoprotein regulation in a dose- and time-dependent manner. The diet stability, reproducibility, and fish palatability were also validated. Fish fed HCD developed hypercholesterolemia as indicated by significantly elevated ApoB-containing lipoproteins (ApoB-LPs) and increased plasma levels of cholesterol and cholesterol esters. Feeding of the HCD to larvae for 8 days produced hepatic steatosis that became more stable and sever after 1 day of fasting and was associated with an opaque liver phenotype (dark under transmitted light). Unlike larvae, adult fish fed HCD for 14 days followed by a 3-day fast did not develop a stable fatty liver phenotype, though the fish had higher ApoB-LP levels in plasma and an upregulated lipogenesis gene fasn in adipose tissue. In conclusion, our HCD zebrafish protocol represents an effective and reliable approach for studying the temporal characteristics of the physiological and biochemical responses to high levels of dietary cholesterol and provides insights into the mechanisms that may underlie fatty liver disease.

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来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
期刊介绍: The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.
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