以油脂乙醇酰胺为基础的膳食补充剂对小鼠饮食性肥胖的肝保护和抗动脉粥样硬化作用。

IF 2.7 Q2 PATHOLOGY
Darya Ivashkevich, Arina Ponomarenko, Igor Manzhulo, Anastasia Egoraeva, Inessa Dyuizen
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引用次数: 0

摘要

背景:在小鼠饮食性肥胖模型中研究了基于油脂乙醇酰胺的膳食补充剂(OEA-DS)的代谢作用。通过2个月的高脂肪、高胆固醇饮食诱导肥胖,导致动物肝脏组织明显形态学改变,血清胆固醇水平升高。肝组织中还观察到促炎细胞因子、氧化应激和肝细胞凋亡水平升高。本研究的目的是研究基于oea的膳食补充剂(OEA-DS)对MASLD发病机理的多个方面产生综合影响的机制,从而证明其具有强大的肝脏保护作用。方法:小鼠饲喂高脂肪、高胆固醇饮食,添加或不添加OEA-DS。分析肝组织和血清胆固醇水平、炎症标志物(CD68、Iba-1、CD163、IL-1β、IL-6、TNFα)、凋亡标志物(Bad、Bax、Bcl-2)、核受体(PPAR-α、PPAR-γ、AdipoR1)、参与脂肪分解的酶(Acox1、Cpt1a)和胆固醇代谢的酶(Ldlr、Furin、Pcsk9)。免疫组织化学、Western blotting和RT-PCR检测蛋白表达和基因转录。结果:OEA-DS使胆固醇水平正常化,炎症标志物(CD68、Iba-1)、促凋亡标志物(Bad、Bax)表达降低,促炎因子(IL-1β、IL-6、TNFα)水平降低。与此同时,核受体PPAR-α和PPAR-γ、脂联素受体1 (AdipoR1)、抗炎(CD163)和抗凋亡(Bcl-2)标志物的表达升高。OEA-DS可诱导肝脏脂解酶(Acox1、Cpt1a)和胆固醇代谢因子(Ldlr、Furin)的表达,同时降低促动脉粥样硬化因子Pcsk9的转录。结论:本研究结果表明,OEA-DS在肥胖相关的肝损伤中具有复杂的作用,包括减少全身炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hepatoprotective and Antiatherosclerotic Effects of Oleoylethanolamide-Based Dietary Supplement in Dietary-Induced Obesity in Mice.

Background: Metabolic effects of oleoylethanolamide-based dietary supplement (OEA-DS) were studied in a model of dietary-induced obesity in mice. Obesity was induced by a 2-month high-fat, high-cholesterol diet, resulting in significant morphological changes in liver tissues and elevated cholesterol levels in the animals' blood serum. Elevated levels of proinflammatory cytokines, oxidative stress, and hepatocyte apoptosis were also observed in the liver tissue. The aim of this study was to examine the mechanisms through which an OEA-based dietary supplement (OEA-DS) exerts a comprehensive influence on multiple aspects of the pathogenesis of MASLD, thereby demonstrating a robust hepatoprotective effect. Methods: mice were fed a high-fat, high-cholesterol diet with or without OEA-DS supplementation. Liver tissues and blood serum were analyzed for cholesterol levels, inflammatory markers (CD68, Iba-1, CD163, IL-1β, IL-6, TNFα), apoptotic markers (Bad, Bax, Bcl-2), nuclear receptors (PPAR-α, PPAR-γ, AdipoR1), and enzymes involved in lipolysis (Acox1, Cpt1a) and cholesterol metabolism (Ldlr, Furin, Pcsk9). Immunohistochemistry, Western blotting, and RT-PCR were used to assess protein expression and gene transcription. Results: administration of OEA-DS normalized cholesterol levels, decreased expression of inflammatory markers (CD68 and Iba-1), pro-apoptotic markers (Bad, Bax) and levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα). In parallel, the expression of nuclear receptors PPAR-α and PPAR-γ, adiponectin receptor 1 (AdipoR1), and anti-inflammatory (CD163) and anti-apoptotic (Bcl-2) markers have risen. OEA-DS administration induced the expression of liver lipolysis enzymes (Acox1, Cpt1a) and cholesterol metabolism factors (Ldlr, Furin), while simultaneously reducing the transcription of the proatherogenic factor Pcsk9. Conclusions: The results of this study suggest a complex action of OEA-DS in obesity-associated liver damage, which includes reduction of systemic inflammation.

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来源期刊
Pathophysiology
Pathophysiology Medicine-Pathology and Forensic Medicine
CiteScore
3.10
自引率
0.00%
发文量
48
期刊介绍: Pathophysiology is an international journal which publishes papers in English which address the etiology, development, and elimination of pathological processes. Contributions on the basic mechanisms underlying these processes, model systems and interdisciplinary approaches are strongly encouraged.
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