源自三文鱼蛋白的低分子量肽可预防LDLR-/-/ApoB100/100小鼠中与肥胖相关的葡萄糖不耐受、炎症和血脂异常。

Low-Molecular-Weight Peptides from Salmon Protein Prevent Obesity-Linked Glucose Intolerance, Inflammation, and Dyslipidemia in LDLR-/-/ApoB100/100 Mice.

作者信息

Chevrier Geneviève, Mitchell Patricia L, Rioux Laurie-Eve, Hasan Fida, Jin Tianyi, Roblet Cyril Roland, Doyen Alain, Pilon Geneviève, St-Pierre Philippe, Lavigne Charles, Bazinet Laurent, Jacques Hélène, Gill Tom, McLeod Roger S, Marette André

机构信息

Department of Medicine, Quebec Heart and Lung Institute, Institute of Nutrition and Functional Foods, and.

Departments of Process Engineering and Applied Science and.

出版信息

J Nutr. 2015 Jul;145(7):1415-22. doi: 10.3945/jn.114.208215. Epub 2015 May 20.

DOI:10.3945/jn.114.208215

PMID:25995281

Abstract

BACKGROUND

We previously reported that fish proteins can alleviate metabolic syndrome (MetS) in obese animals and human subjects.

OBJECTIVES

We tested whether a salmon peptide fraction (SPF) could improve MetS in mice and explored potential mechanisms of action.

METHODS

ApoB(100) only, LDL receptor knockout male mice (LDLR(-/-)/ApoB(100/100)) were fed a high-fat and -sucrose (HFS) diet (25 g/kg sucrose). Two groups were fed 10 g/kg casein hydrolysate (HFS), and 1 group was additionally fed 4.35 g/kg fish oil (FO; HFS+FO). Two other groups were fed 10 g SPF/kg (HFS+SPF), and 1 group was additionally fed 4.35 g FO/kg (HFS+SPF+FO). A fifth (reference) group was fed a standard feed pellet diet. We assessed the impact of dietary treatments on glucose tolerance, adipose tissue inflammation, lipid homeostasis, and hepatic insulin signaling. The effects of SPF on glucose uptake, hepatic glucose production, and inducible nitric oxide synthase activity were further studied in vitro with the use of L6 myocytes, FAO hepatocytes, and J774 macrophages.

RESULTS

Mice fed HFS+SPF or HFS+SPF+FO diets had lower body weight (protein effect, P = 0.024), feed efficiency (protein effect, P = 0.018), and liver weight (protein effect, P = 0.003) as well as lower concentrations of adipose tissue cytokines and chemokines (protein effect, P ≤ 0.003) compared with HFS and HFS+FO groups. They also had greater glucose tolerance (protein effect, P < 0.001), lower activation of the mammalian target of rapamycin complex 1/S6 kinase 1/insulin receptor substrate 1 (mTORC1/S6K1/IRS1) pathway, and increased insulin signaling in liver compared with the HFS and HFS+FO groups. The HFS+FO, HFS+SPF, and HFS+SPF+FO groups had lower plasma triglycerides (protein effect, P = 0.003; lipid effect, P = 0.002) than did the HFS group. SPF increased glucose uptake and decreased HGP and iNOS activation in vitro.

CONCLUSIONS

SPF reduces obesity-linked MetS features in LDLR(-/-)/ApoB(100/100) mice. The anti-inflammatory and glucoregulatory properties of SPF were confirmed in L6 myocytes, FAO hepatocytes, and J774 macrophages.

摘要

背景

我们之前报道过，鱼类蛋白可缓解肥胖动物和人类受试者的代谢综合征（MetS）。

目的

我们测试了鲑鱼肽组分（SPF）是否能改善小鼠的代谢综合征，并探索其潜在作用机制。

方法

仅载脂蛋白B（100）的低密度脂蛋白受体敲除雄性小鼠（LDLR（-/-）/ApoB（100/100））喂食高脂肪高蔗糖（HFS）饮食（25 g/kg蔗糖）。两组喂食10 g/kg酪蛋白水解物（HFS），一组额外喂食4.35 g/kg鱼油（FO；HFS+FO）。另外两组喂食10 g SPF/kg（HFS+SPF），一组额外喂食4.35 g FO/kg（HFS+SPF+FO）。第五组（参照组）喂食标准饲料颗粒饮食。我们评估了饮食处理对葡萄糖耐量、脂肪组织炎症、脂质稳态和肝脏胰岛素信号传导的影响。使用L6肌细胞、FAO肝细胞和J774巨噬细胞在体外进一步研究了SPF对葡萄糖摄取、肝脏葡萄糖生成和诱导型一氧化氮合酶活性的影响。

结果

与HFS组和HFS+FO组相比，喂食HFS+SPF或HFS+SPF+FO饮食的小鼠体重更低（蛋白质效应，P = 0.024）、饲料效率更低（蛋白质效应，P = 0.018）、肝脏重量更低（蛋白质效应，P = 0.003），脂肪组织细胞因子和趋化因子浓度也更低（蛋白质效应，P≤0.003）。与HFS组和HFS+FO组相比，它们还具有更好的葡萄糖耐量（蛋白质效应，P < 0.001）、哺乳动物雷帕霉素靶蛋白复合物1/核糖体蛋白S6激酶1/胰岛素受体底物1（mTORC1/S6K1/IRS1）通路的激活程度更低，且肝脏中的胰岛素信号传导增强。HFS+FO组、HFS+SPF组和HFS+SPF+FO组的血浆甘油三酯水平低于HFS组（蛋白质效应，P = 0.003；脂质效应，P = 0.002）。SPF在体外增加了葡萄糖摄取，降低了肝脏葡萄糖生成和诱导型一氧化氮合酶的激活。