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来自鲣鱼(Katsuwonus pelamis)鱼骨的胶原蛋白肽:组成、特性及改善高脂饮食诱导的非酒精性脂肪性肝病的机制

Collagen peptides from Skipjack tuna (Katsuwonus pelamis) bones: Composition, characterization, and mechanism of high-fat diet-induced NAFLD amelioration.

作者信息

Jiang Yu-Lin, Zhang Shuang-Yi, Wang Bin, Zeng Yu-Hui, Xu Li, Chi Chang-Feng

机构信息

Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.

Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.

出版信息

Food Res Int. 2025 Nov;219:117114. doi: 10.1016/j.foodres.2025.117114. Epub 2025 Jul 28.

DOI:10.1016/j.foodres.2025.117114
PMID:40922180
Abstract

This study aimed to analyze the amino acid composition and characterize the sequences of collagen peptides from Skipjack tuna bones (TBCPs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and further investigate the function and mechanism of action of TBCPs in nonalcoholic fatty liver disease (NAFLD). The results showed that TBCPs contain 16 types of amino acids, among which glycine is the most abundant, and hydrophobic amino acids account for 40.75 %. Moreover, a total of twenty-eight active peptide sequences with an ALC ≥ 95 % were identified from TBCPs. In vivo test results revealed that TBCPs can reverse weight gain, liver lobular injury, hepatic cord disorders, and increased inflammatory cell levels in mice with high-fat diet (HFD)-induced NAFLD. Moreover, TBCPs contributed to reducing the number and size of lipid droplets and vacuoles in liver slices and decreased the degree of lipid degeneration. The mechanistic studies indicated that TBCPs can promote AMPK phosphorylation, reduce sterol synthesis, and decrease SREBP-1c synthesis, thereby reducing fat synthesis and decreasing the levels of TG, TC, AST, and ALT. Additionally, TBCPs can promote lipid β-oxidation by increasing PPAR-α and CPT-1 levels. Moreover, TBCPs can increase antioxidant levels to counteract oxidative stress by activating the Nrf2 pathway to increase the protein expression of HO-1 and NQO1; increase the activity of SOD, GSH-Px, and CAT; and reduce the MDA content. Moreover, TBCPs can alleviate the inflammatory response by reducing the expression levels of TLR4, MyD88, TNF-α, and IL-6. Therefore, TBCPs may be considered a beneficial dietary supplement for maintaining liver health.

摘要

本研究旨在通过液相色谱-串联质谱法(LC-MS/MS)分析鲣鱼鱼骨胶原蛋白肽(TBCPs)的氨基酸组成并表征其序列,并进一步研究TBCPs在非酒精性脂肪性肝病(NAFLD)中的功能及作用机制。结果表明,TBCPs含有16种氨基酸,其中甘氨酸含量最高,疏水氨基酸占40.75%。此外,从TBCPs中鉴定出总共28条活性肽序列,其氨基酸序列覆盖率(ALC)≥95%。体内试验结果显示,TBCPs可逆转高脂饮食(HFD)诱导的NAFLD小鼠的体重增加、肝小叶损伤、肝索紊乱以及炎症细胞水平升高。此外,TBCPs有助于减少肝切片中脂滴和空泡的数量及大小,并降低脂质变性程度。机制研究表明,TBCPs可促进AMPK磷酸化,减少固醇合成,并降低SREBP-1c合成,从而减少脂肪合成并降低甘油三酯(TG)、总胆固醇(TC)、天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平。此外,TBCPs可通过提高过氧化物酶体增殖物激活受体α(PPAR-α)和肉碱/有机阳离子转运体1(CPT-1)水平来促进脂质β-氧化。此外,TBCPs可通过激活Nrf2途径来增加血红素加氧酶-1(HO-1)和醌氧化还原酶1(NQO1)的蛋白表达,从而提高抗氧化剂水平以对抗氧化应激;提高超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)的活性;并降低丙二醛(MDA)含量。此外,TBCPs可通过降低Toll样受体4(TLR4)、髓样分化因子88(MyD88)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达水平来减轻炎症反应。因此,TBCPs可被视为维持肝脏健康有益的膳食补充剂。

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