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高脂饮食在不肥胖的情况下通过诱导 VEGF-C 在小鼠淋巴水肿模型中增加淋巴管生成。

A High-Fat Diet in the Absence of Obesity Increases Lymphangiogenesis by Inducing VEGF-C in a Murine Lymphedema Model.

机构信息

From the Department of Plastic and Reconstructive Surgery, Keimyung University School of Medicine.

Departments of Pathology.

出版信息

Plast Reconstr Surg. 2023 Jul 1;152(1):87-96. doi: 10.1097/PRS.0000000000010037. Epub 2023 Jun 29.

DOI:10.1097/PRS.0000000000010037
PMID:36730763
Abstract

BACKGROUND

Many researchers have attempted to induce lymphangiogenesis for the treatment of lymphedema. However, most previous studies had limited clinical usefulness. A high-fat diet (HFD) increases serum β-hydroxybutyrate (β-OHB) levels, which can stimulate lymphangiogenesis. The authors hypothesized that an HFD will ameliorate lymphedema through enhanced lymphangiogenesis.

METHODS

The effects of β-OHB on the lymphangiogenic process in human dermal lymphatic endothelial cells were analyzed. A mouse tail lymphedema model was used to evaluate the effects of an HFD on lymphedema. Experimental mice were fed an HFD (45% kcal as fat, 20% as protein, and 35% as carbohydrates) for 4 weeks. Tail volume was measured using the truncated cone formula. Biopsy specimens were taken 6 weeks after surgical induction of lymphedema.

RESULTS

In human dermal lymphatic endothelial cells, treatment with 20 mM of β-OHB increased cell viability ( P = 0.008), cell migration ( P = 0.011), tube formation ( P = 0.005), and VEGF-C mRNA and protein expression ( P < 0.001) compared with controls. HFD feeding decreased tail volume by 14.3% and fibrosis by 15.8% ( P = 0.027), and increased the lymphatic vessel density ( P = 0.022) and VEGF-C protein expression ( P = 0.005) compared with those of operated, standard chow diet-fed mice.

CONCLUSIONS

The authors' findings demonstrated that β-OHB promoted lymphatic endothelial cell function and increased VEGF-C mRNA and protein expression. When mice with tail lymphedema were fed an HFD, volume and fibrosis of the tail decreased. Therefore, the authors' findings suggest that an HFD can be a successful novel dietary approach to treating lymphedema.

CLINICAL RELEVANCE STATEMENT

Lymphatic regeneration after vascularized lymph node transfer can be augmented when a high-fat diet is used in conjunction with vascularized lymph node transfer.

摘要

背景

许多研究人员试图诱导淋巴管生成来治疗淋巴水肿。然而,大多数先前的研究临床实用性有限。高脂肪饮食(HFD)会增加血清β-羟基丁酸(β-OHB)水平,从而刺激淋巴管生成。作者假设 HFD 通过增强淋巴管生成来改善淋巴水肿。

方法

分析了β-OHB 对人真皮淋巴内皮细胞淋巴管生成过程的影响。使用小鼠尾淋巴水肿模型评估 HFD 对淋巴水肿的影响。实验小鼠喂养 HFD(45%热量来自脂肪,20%来自蛋白质,35%来自碳水化合物)4 周。使用截断圆锥公式测量尾体积。在手术诱导淋巴水肿 6 周后采集活检标本。

结果

在人真皮淋巴内皮细胞中,与对照组相比,用 20 mM 的β-OHB 处理可增加细胞活力(P=0.008)、细胞迁移(P=0.011)、管形成(P=0.005)和 VEGF-C mRNA 和蛋白表达(P<0.001)。与接受手术和标准饲料喂养的小鼠相比,HFD 喂养使尾巴体积减少 14.3%,纤维化减少 15.8%(P=0.027),增加了淋巴管密度(P=0.022)和 VEGF-C 蛋白表达(P=0.005)。

结论

作者的研究结果表明,β-OHB 促进了淋巴管内皮细胞的功能,并增加了 VEGF-C mRNA 和蛋白的表达。当患有尾部淋巴水肿的小鼠喂食 HFD 时,尾巴的体积和纤维化减少。因此,作者的研究结果表明,HFD 可能是治疗淋巴水肿的一种成功的新型饮食方法。

临床相关性声明

在进行血管化淋巴结转移时,如果联合使用高脂肪饮食,淋巴再生可以增强。

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