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在早期代谢功能障碍相关脂肪性肝病C57BL/6N小鼠模型中,补充脱脂牛奶可减轻肝脏脂质蓄积并改善肝脏脂质代谢。

Nonfat Milk Supplementation Mitigates Hepatic Lipid Accumulation and Improves Hepatic Lipid Metabolism in an Early Metabolic Dysfunction-Associated Steatotic Liver Disease C57BL/6N Mouse Model.

作者信息

Berg Emily, Moftah Salma, Yuzbashian Emad, Chan Catherine B

机构信息

Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Department of Agriculture, Food and Nutrition Sciences, Faculty of Agriculture, Life, and Environmental Science, University of Alberta, Edmonton, Alberta, Canada.

出版信息

J Nutr. 2025 Nov;155(11):3850-3860. doi: 10.1016/j.tjnut.2025.09.020. Epub 2025 Sep 26.

DOI:10.1016/j.tjnut.2025.09.020
PMID:41015295
Abstract

BACKGROUND

Dairy products may mitigate metabolic dysfunction-associated steatotic liver disease (MASLD) progression, but the role of dairy fat is unclear.

OBJECTIVES

This animal trial compared MASLD-related outcomes after feeding nonfat milk (NFM) or whole-fat milk (WFM) in a high-fat diet (HFD)-induced MASLD mouse model.

METHODS

Male C57BL/6N mice were fed a HFD (45% kcal fat; n = 40) for 9 wk. During the last 8 wk, 2 randomly selected groups additionally consumed 0.425 mL NFM (0 g% fat; n = 8) or WFM (3.25 g% fat; n = 12), from a small dish, 5 d/wk. A low-fat diet group (10% kcal fat; n = 20) served as a reference. The metabolic phenotype and liver lipid metabolism pathways were studied and compared by 1-way analysis of variance; P ≤ 0.05 was considered significant.

RESULTS

NFM reduced body weight (BW) gain (46 ± 2.5 compared with 61 ± 3.5 %BW, P < 0.01) and hepatic triglyceride content (46.0 ± 10.4 compared with 71.7 ± 14.4 mg/g, P <0.05) compared with HFD. Immunoblotting revealed that NFM feeding increased hepatic mitochondrial complex abundance (P < 0.05) compared with WFM. Compared with NFM, WFM had higher triglyceride content (69.2 ± 16.5 compared with 46.0 ± 10.4 mg/g, P < 0.05) but reduced liver area covered by lipid droplets in comparison with HFD (6.49 ± 2.75 compared with 13.61 ± 2.75% standard area, P = 0.051). De novo lipogenesis enzymes, fatty acid synthase (1.33 ± 0.56 compared with 0.76 ± 0.56 AU, P < 0.05) and phosphorylated acetyl-CoA carboxylase (1.65 ± 0.49 compared with 0.02 ± 0.49 AU, P < 0.05) were increased compared with NFM. Carnitine palmitoyl transferase 1α (1.48 ± 0.19 compared with 1.00 ± 0.19 AU, P < 0.05) was increased in WFM compared with HFD animals, and Opa1 mRNA expression was increased in WFM (1.26 ± 0.21 compared with 0.66 ± 0.21 AU, P < 0.05) compared with the NFM group.

CONCLUSIONS

Compared with WFM, NFM mice had greater benefits in mitigating MASLD progression through increased capacity for oxidative phosphorylation and fatty acid export, leading to reduced hepatic fat accumulation.

摘要

背景

乳制品可能减轻代谢功能障碍相关脂肪性肝病(MASLD)的进展,但乳脂肪的作用尚不清楚。

目的

本动物试验比较了在高脂饮食(HFD)诱导的MASLD小鼠模型中,喂食脱脂牛奶(NFM)或全脂牛奶(WFM)后与MASLD相关的结果。

方法

雄性C57BL/6N小鼠喂食HFD(45%千卡脂肪;n = 40)9周。在最后8周期间,2个随机选择的组另外每周5天从小盘中摄入0.425 mL NFM(0 g%脂肪;n = 8)或WFM(3.25 g%脂肪;n = 12)。低脂饮食组(10%千卡脂肪;n = 20)作为对照。通过单因素方差分析研究和比较代谢表型和肝脏脂质代谢途径;P≤0.05被认为具有统计学意义。

结果

与HFD组相比,NFM组体重(BW)增加减少(46±2.5%BW,而HFD组为61±3.5%BW,P<0.01),肝甘油三酯含量降低(46.0±10.4 mg/g,而HFD组为71.7±14.4 mg/g,P<0.05)。免疫印迹显示,与WFM组相比,喂食NFM可增加肝脏线粒体复合物丰度(P<0.05)。与NFM组相比,WFM组甘油三酯含量更高(69.2±16.5 mg/g,而NFM组为46.0±10.4 mg/g,P<0.05),但与HFD组相比,脂质滴覆盖的肝脏面积减少(6.49±2.75%标准面积,而HFD组为13.61±2.75%标准面积,P = 0.051)。与NFM组相比,WFM组从头脂肪生成酶、脂肪酸合酶(1.33±0.56 AU,而NFM组为0.76±0.56 AU,P<0.05)和磷酸化乙酰辅酶A羧化酶(1.65±0.49 AU,而NFM组为0.02±0.49 AU,P<0.05)增加。与HFD组动物相比,WFM组肉碱棕榈酰转移酶1α增加(1.48±0.19 AU,而HFD组为1.00±0.19 AU,P<0.05),与NFM组相比,WFM组Opa1 mRNA表达增加(1.26±0.21 AU,而NFM组为0.66±0.21 AU,P<0.05)。

结论

与WFM组相比,NFM组小鼠通过增加氧化磷酸化和脂肪酸输出能力,在减轻MASLD进展方面具有更大益处,从而减少肝脏脂肪堆积。

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