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钝顶螺旋藻肽负载纳米脂质体通过AMPK信号通路影响氧化还原稳态和脂质代谢减轻雄性Wistar大鼠肝脏脂质积累

Spirulina platensis Peptide-Loaded Nanoliposomes Alleviate Hepatic Lipid Accumulation in Male Wistar Rats by Influencing Redox Homeostasis and Lipid Metabolism via the AMPK Signaling Pathway.

作者信息

Karimzadeh Katayoon, Unniappan Suraj, Zahmatkesh Asgar

机构信息

Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada.

出版信息

Appl Biochem Biotechnol. 2025 Mar;197(3):1696-1725. doi: 10.1007/s12010-024-05089-w. Epub 2024 Nov 27.

Abstract

Spirulina platensis low-molecular-weight peptides (SP) have been reported to exhibit antioxidant and hepatoprotective properties. However, the limited bioavailability and solubility of SPs limit their potential applications. In this study, to examine the potential anti-obesity effects and underlying mechanisms of SPs, high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) model rats were treated with SPs and SP-loaded nanoliposomes. Furthermore, hepatic biochemical parameters, inflammatory markers, histopathological changes, and genes involved in AMPK signaling were analyzed. SP-loaded nanoliposomes demonstrated a spherical shape with slower and sustained SP release. SP and SP-loaded nanoliposomes mitigated hepatic damage by lowering serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and increasing hepatic antioxidant enzymes, which are manifested in improving histopathological findings. In addition, notably, SP-loaded nanoliposomes downregulated lipogenic fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) in the liver. Meanwhile, an upregulation of phosphorylated AMP-activated protein kinase (P-AMPK), lipid acid oxidation-related genes carnitine palmitoyltransferase-1 (CPT-1), and peroxisome proliferator-activated receptor alpha (PPAR-α) was found in the rat liver. This data implies that SP and SP-loaded nanoliposomes exhibit protective potential in rats against the HFD-induced NAFLD, which is mediated through the activation of the AMPK signaling pathway.

摘要

据报道,钝顶螺旋藻低分子量肽(SP)具有抗氧化和肝脏保护特性。然而,SP有限的生物利用度和溶解度限制了它们的潜在应用。在本研究中,为了研究SP的潜在抗肥胖作用及其潜在机制,用SP和负载SP的纳米脂质体处理高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)模型大鼠。此外,还分析了肝脏生化参数、炎症标志物、组织病理学变化以及参与AMPK信号传导的基因。负载SP的纳米脂质体呈球形,SP释放缓慢且持续。SP和负载SP的纳米脂质体通过降低血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)以及增加肝脏抗氧化酶来减轻肝脏损伤,这在改善组织病理学结果中得以体现。此外,值得注意的是,负载SP的纳米脂质体下调了肝脏中脂肪生成相关的脂肪酸合酶(FAS)和固醇调节元件结合蛋白-1c(SREBP-1c)。同时,在大鼠肝脏中发现磷酸化的AMP激活蛋白激酶(P-AMPK)、脂肪酸氧化相关基因肉碱棕榈酰转移酶-1(CPT-1)和过氧化物酶体增殖物激活受体α(PPAR-α)上调。这些数据表明,SP和负载SP的纳米脂质体在大鼠中对高脂饮食诱导的NAFLD具有保护潜力,这是通过激活AMPK信号通路介导的。

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