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不同高脂肪饮食对代谢、炎症标志物、菌群失调和肝组织学的影响:基于 NASH 大鼠模型诱导饮食的研究。

Impact of multiple different high-fat diets on metabolism, inflammatory markers, dysbiosis, and liver histology: study on NASH rat model induced diet.

机构信息

Doctoral Program of Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Jl. Veteran, 65145, Indonesia.

Department of Clinical Microbiology, Faculty of Medicine, Universitas Brawijaya, Malang, Jl. Veteran, 65145, Indonesia.

出版信息

F1000Res. 2023 Dec 12;12:180. doi: 10.12688/f1000research.129645.2. eCollection 2023.

Abstract

BACKGROUND

The spectrum of non-alcoholic fatty liver disease (NAFLD), known as non-alcoholic steatohepatitis (NASH), can lead to advanced liver disease. It is known that a variety of diets play a significant role in the development of NAFLD/NASH. The goal of this study was to determine the most appropriate composition of diet to induce NASH in an animal model.

METHODS

This research used strain Wistar (n=27), which were divided into four groups and given each diet for 12 weeks: normal diet (ND, n=7), high-fat diet (HFD, n=6), western diet (WD, n=7), and high-fat-high-fructose diet (HFHFD, n=7). Subjects were monitored for changes in body weight. Blood samples were collected for biochemical analysis, including (LDL), triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatic lipase, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and lipopolysaccharide (LPS). Fecal samples were taken for (SCFA) analysis. Liver histology was assessed using NAS (NAFLD activity score). A statistical comparison test was carried out using the one-way ANOVA or Kruskal-Wallis test.

RESULTS

The highest average body weight was observed in the WD group (346.14 g). Liver enzymes, LDL, triglyceride, propionic acid, and acetic acid did not show significantly differences among the groups. TNF-α, IL-6, and hepatic lipase were significant (p = 0.000; p = 0.000; p = 0.004) and the highest level recorded in the HFD group. Butyrate acid level also showed significances (p = 0.021) with the lowest concentration seen in the HFHFD group (4.77 mMol/g). Only WD and HFHFD had a NAS ≥ 5 (14% and 14%). The highest percentage of borderline NAS was found in WD (57%).

CONCLUSIONS

WD feeding is the most appropriate diet type to induce NASH in rats as it influences metabolic, inflammatory, dysbiosis, and liver histology of rats.

摘要

背景

非酒精性脂肪性肝病(NAFLD)的谱,称为非酒精性脂肪性肝炎(NASH),可导致晚期肝病。已知各种饮食在 NAFLD/NASH 的发展中起着重要作用。本研究的目的是确定最适合的饮食组合,以在动物模型中诱导 NASH。

方法

本研究使用 Wistar 品系(n=27),将其分为四组,并分别给予以下饮食 12 周:正常饮食(ND,n=7)、高脂肪饮食(HFD,n=6)、西方饮食(WD,n=7)和高脂肪高果糖饮食(HFHFD,n=7)。监测体重变化。采集血样进行生化分析,包括(LDL)、甘油三酯、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、肝脂酶、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和脂多糖(LPS)。采集粪便样本进行(SCFA)分析。采用 NAS(NAFLD 活动评分)评估肝组织学。使用单向方差分析或 Kruskal-Wallis 检验进行统计比较检验。

结果

WD 组体重平均最高(346.14g)。各组肝酶、LDL、甘油三酯、丙酸和乙酸无显著差异。TNF-α、IL-6 和肝脂酶显著(p=0.000;p=0.000;p=0.004),HFD 组水平最高。丁酸水平也具有显著性(p=0.021),HFHFD 组浓度最低(4.77mMol/g)。只有 WD 和 HFHFD 的 NAS≥5(14%和 14%)。WD 的边界 NAS 百分比最高(57%)。

结论

WD 喂养是诱导大鼠 NASH 的最合适饮食类型,因为它影响大鼠的代谢、炎症、菌群失调和肝组织学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c79d/11369670/2a903ae9a0cd/f1000research-12-159829-g0000.jpg

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