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通过负载番茄红素的纳米脂质体增强生化和基因组途径:缓解非酒精性脂肪性肝病肥胖大鼠的胰岛素抵抗、肝脂肪变性和自噬:涉及 SMO、GLI-1 和 PTCH-1 基因。

Enhancement of biochemical and genomic pathways through lycopene-loaded nano-liposomes: Alleviating insulin resistance, hepatic steatosis, and autophagy in obese rats with non-alcoholic fatty liver disease: Involvement of SMO, GLI-1, and PTCH-1 genes.

机构信息

Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44511 Zagazig, Egypt.

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.

出版信息

Gene. 2023 Oct 20;883:147670. doi: 10.1016/j.gene.2023.147670. Epub 2023 Jul 27.

Abstract

Non-alcoholic fatty liver (NAFL) is a prevalent hepatic disorder of global significance that can give rise to severe complications. This research endeavor delves into the potential of nano-liposomal formulated Lycopene (Lip-Lyco) in averting the development of obesity and insulin resistance, both of which are major underlying factors contributing to NAFL. The investigation further scrutinizes the impact of Lip-Lyco on intricate cellular pathways within the liver tissue of rats induced with NAFL, specifically focusing on the progression of steatosis and fibrosis. To establish an obesity-NAFL model, twenty rats were subjected to a high-fat diet (HFD) for a duration of twelve weeks, after which they received an oral treatment of Lip-Lyco (10mg/kg) for an additional eight weeks. Another group of sixteen non-obese rats were subjected to treatment with or without Lip-Lyco, serving as a control for comparison. Results: The rats on a hypercaloric diet had high body mass index (BMI) and insulin resistance, reflected in disturbed serum adipokines and lipid profiles. Oxidative stress, inflammation, and apoptosis were evident in hepatic tissue, and the autophagic process in hepatocytes was inhibited. Additionally, the hedgehog pathway was activated in the liver tissue of NAFL group. Lip-Lyco was found to counteract all these aspects of NAFL pathogenesis. Lip-Lyco exhibited antioxidant, anti-inflammatory, hypoglycemic, antiapoptotic, autophagy-inducing, and Hedgehog signaling inhibitory effects. This study concludes that Lip-Lyco, a natural compound, has promising therapeutic potential in combating NAFLdisease. However, more experimental and clinical studies are required to confirm the effectiveness of lycopene in treating NAFLdisease.

摘要

非酒精性脂肪性肝病(NAFL)是一种具有全球意义的常见肝脏疾病,可导致严重并发症。本研究探讨了纳米脂质体包封的番茄红素(Lip-Lyco)在预防肥胖和胰岛素抵抗中的潜力,肥胖和胰岛素抵抗是导致 NAFL 的两个主要潜在因素。研究进一步研究了 Lip-Lyco 对 NAFL 大鼠肝组织中复杂细胞途径的影响,特别是关注脂肪变性和纤维化的进展。为了建立肥胖性 NAFL 模型,将 20 只大鼠给予高脂肪饮食(HFD)十二周,然后再给予 Lip-Lyco(10mg/kg)口服治疗八周。另一组 16 只非肥胖大鼠给予或不给予 Lip-Lyco 治疗,作为对照组进行比较。结果:高热量饮食组大鼠体重指数(BMI)和胰岛素抵抗较高,表现在血清脂肪因子和脂质谱紊乱。肝组织中存在氧化应激、炎症和细胞凋亡,肝细胞自噬过程受到抑制。此外,NAFL 组肝组织中 Hedgehog 通路被激活。Lip-Lyco 被发现可逆转 NAFL 发病机制的所有这些方面。Lip-Lyco 具有抗氧化、抗炎、降血糖、抗凋亡、诱导自噬和 Hedgehog 信号抑制作用。本研究得出结论,Lip-Lyco 作为一种天然化合物,在治疗 NAFL 疾病方面具有潜在的治疗潜力。然而,需要更多的实验和临床研究来证实番茄红素在治疗 NAFL 疾病中的有效性。

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