Ivashkevich Darya, Ponomarenko Arina, Manzhulo Igor, Egoraeva Anastasia, Dyuizen Inessa
A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevskogo Str., 17, 690041 Vladivostok, Russia.
Pathophysiology. 2025 Apr 18;32(2):16. doi: 10.3390/pathophysiology32020016.
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. 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. 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. The results of this study suggest a complex action of OEA-DS in obesity-associated liver damage, which includes reduction of systemic inflammation.
在饮食诱导的小鼠肥胖模型中研究了基于油酰乙醇胺的膳食补充剂（OEA-DS）的代谢作用。通过为期2个月的高脂、高胆固醇饮食诱导肥胖，导致肝脏组织出现显著的形态学变化，并且动物血清中的胆固醇水平升高。在肝脏组织中还观察到促炎细胞因子水平升高、氧化应激和肝细胞凋亡。本研究的目的是研究基于OEA的膳食补充剂（OEA-DS）对MAFLD发病机制多个方面产生全面影响的机制，从而证明其强大的肝脏保护作用。给小鼠喂食含或不含OEA-DS补充剂的高脂、高胆固醇饮食。分析肝脏组织和血清中的胆固醇水平、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）以及参与脂肪分解（Acox1、Cpt1a）和胆固醇代谢（Ldlr、Furin、Pcsk9）的酶。采用免疫组织化学、蛋白质印迹法和逆转录-聚合酶链反应来评估蛋白质表达和基因转录。给予OEA-DS可使胆固醇水平正常化，降低炎症标志物（CD68和Iba-1）、促凋亡标志物（Bad、Bax）的表达以及促炎细胞因子（IL-1β、IL-6、TNFα）的水平。同时，核受体PPAR-α和PPAR-γ、脂联素受体1（AdipoR1）以及抗炎（CD163）和抗凋亡（Bcl-2）标志物的表达有所升高。给予OEA-DS可诱导肝脏脂肪分解酶（Acox1、Cpt1a）和胆固醇代谢因子（Ldlr、Furin）的表达，同时减少促动脉粥样硬化因子Pcsk9的转录。本研究结果表明OEA-DS在肥胖相关肝损伤中具有复杂作用，其中包括减轻全身炎症。
