神经紧张素受体-1 拮抗剂 SR48692 调节高脂饮食诱导的小鼠非酒精性脂肪肝发病机制

IF 1.8 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY European Journal of Lipid Science and Technology Pub Date : 2024-04-05 DOI:10.1002/ejlt.202300162
Himanshu Pal, Pradeep Verma, Banalata Mohanty
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摘要

本研究探讨了神经紧张素受体-1(NTSR1)拮抗剂 SR48692 在调节高脂饮食(HFD)诱发的非酒精性脂肪肝(NAFLD)方面的疗效。高脂饮食会增加 NTS 的分泌,从而通过 NTSR1/NTSR2/NTSR3 受体促进胃肠道(GIT)对脂肪的吸收。从胃肠道吸收的脂肪通过肝-门系统到达肝脏,在肝脏积聚,导致非酒精性脂肪肝。瑞士白化小鼠(8 周)分两批饲养,分别喂食标准饮食(SD)和高脂饮食 4 周,然后分为六组:I组(SD)和II组(HFD)腹腔注射0.9%生理盐水(载体),III组:低剂量拮抗剂(100 µg kg-1体重:HFD+SR48692L),IV组:高剂量(400 µg kg-1体重:HFD+SR48692H),V组(SD+SR48692L)和VI组(SD+SR48692H)。从组织学和血浆转氨酶中可以看出,SR48692L 对高纤维食物喂养的小鼠在防止脂质吸收和减少氧化应激方面有部分疗效。相反,使用 SR48692H 剂量则会产生有害影响。其他信号通路(NTS-NTSR2、NTS-NTSR3)参与脂质吸收可能是产生部分疗效的原因。SR48692H 的不良反应可能是由于拮抗剂的剂量反应效应不同造成的:实际应用:高密度脂蛋白胆固醇诱导的高脂血症和非酒精性脂肪肝与 NTS 分泌增强有关。由于 NTS 能促进脂肪的吸收,因此用拮抗剂阻断其受体可能会对 HFD 诱导的非酒精性脂肪肝产生疗效。这项关于 NTSR1 拮抗剂 SR48692 的研究为其预防高脂血症提供了一些证据;针对其他受体(NTSR2、NTSR3)的进一步研究对于了解 NTS 拮抗剂对非酒精性脂肪肝的疗效至关重要。
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Neurotensin receptor-1 antagonist SR48692 modulation of high-fat diet–induced pathogenesis of NAFLD in mice

This study investigates the efficacy of the antagonist of neurotensin receptor-1 (NTSR1) SR48692 in modulating the high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). HFD increases NTS secretion, which enhances fat absorption from the gastrointestinal tract (GIT) via receptors NTSR1/NTSR2/NTSR3. Absorbed fat from the GIT via hepatic-portal system reaches the liver, where it gets accumulated to cause NAFLD. Swiss albino mice (8 weeks) were maintained in two batches fed standard diet (SD) and HFD for 4 weeks, then divided into six groups: Group I (SD) and Group II (HFD) administered intraperitoneally 0.9% saline (vehicle), Group III: low dose of antagonist (100 µg kg−1 bw: HFD+SR48692L), Group IV: high dose (400 µg kg−1 bw: HFD+SR48692H), Group V (SD+SR48692L), and Group VI (SD+SR48692H). SR48692L treatment in HFD-fed mice showed partial efficacy in preventing lipid absorption and reducing oxidative stress, as reflected in histology and plasma transaminases. Contrarily, with SR48692H dose, the effects were detrimental. Involvement of other signaling pathways (NTS-NTSR2, NTS-NTSR3) in lipid absorption might be the reason of partial efficacy. The adverse effects with the SR48692H might be due to the differential dose–response effect of the antagonist.

Practical Application: HFD-induced hyperlipidemia and NAFLD are linked to enhanced NTS secretion. As NTS enhances fat absorption, blocking its receptors with antagonists might provide efficacy against HFD-induced NAFLD. This study with NTSR1 antagonist SR48692 provides some evidence of its in preventing hyperlipidemia; further studies targeting other receptors (NTSR2, NTSR3) are essential for understanding the therapeutic efficacy of the NTS antagonists for NAFLD.

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来源期刊
CiteScore
5.50
自引率
0.00%
发文量
101
审稿时长
6-16 weeks
期刊介绍: The European Journal of Lipid Science and Technology is a peer-reviewed journal publishing original research articles, reviews, and other contributions on lipid related topics in food science and technology, biomedical science including clinical and pre-clinical research, nutrition, animal science, plant and microbial lipids, (bio)chemistry, oleochemistry, biotechnology, processing, physical chemistry, and analytics including lipidomics. A major focus of the journal is the synthesis of health related topics with applied aspects. Following is a selection of subject areas which are of special interest to EJLST: Animal and plant products for healthier foods including strategic feeding and transgenic crops Authentication and analysis of foods for ensuring food quality and safety Bioavailability of PUFA and other nutrients Dietary lipids and minor compounds, their specific roles in food products and in nutrition Food technology and processing for safer and healthier products Functional foods and nutraceuticals Lipidomics Lipid structuring and formulations Oleochemistry, lipid-derived polymers and biomaterials Processes using lipid-modifying enzymes The scope is not restricted to these areas. Submissions on topics at the interface of basic research and applications are strongly encouraged. The journal is the official organ the European Federation for the Science and Technology of Lipids (Euro Fed Lipid).
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Cover Picture: Eur. J. Lipid Sci. Technol. 11/2024 Editorial Board: Eur. J. Lipid Sci. Technol. 11/2024 Contents: Eur. J. Lipid Sci. Technol. 11/2024 One step beyond for CNSL-based plasticizers for PVC: Use of cardol Cover Picture: Eur. J. Lipid Sci. Technol. 10/2024
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