饮食中的矢车菊素-3-葡萄糖苷通过对肝脏激素 FGF21 的作用减轻高脂饮食诱导的小鼠体重增加和葡萄糖耐量受损。
Dietary Cyanidin-3-Glucoside Attenuates High-Fat-Diet-Induced Body-Weight Gain and Impairment of Glucose Tolerance in Mice via Effects on the Hepatic Hormone FGF21.
机构信息
Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Department of Physiology, University of Toronto, Toronto, Canada.
出版信息
J Nutr. 2020 Aug 1;150(8):2101-2111. doi: 10.1093/jn/nxaa140.
BACKGROUND
Dietary polyphenols including anthocyanins target multiple organs.
OBJECTIVE
We aimed to assess the involvement of glucagon-like peptide 1 (GLP-1), leptin, insulin and fibroblast growth factor 21 (FGF21) in mediating metabolic beneficial effects of purified anthocyanin cyanidin-3-glucoside (Cy3G).
METHODS
Intestinal proglucagon gene (Gcg; encoding GLP-1) and liver Fgf21 expression were assessed in 6-wk-old male C57BL-6J mice fed a low-fat-diet (LFD; 10% of energy from fat), alone or with 1.6 mg Cy3G/L in drinking water for 3 wk [experiment (Exp.) 1; n = 5/group]. Similar mice were fed the LFD or a high-fat diet (HFD; 60% energy from fat) with or without Cy3G for 20 wk. Half of the mice administered Cy3G also received 4 broad-spectrum antibiotics (ABs) in drinking water between weeks 11 and 14, for a total of 6 groups (n = 8/group). Metabolic tolerance tests were conducted between weeks 2 and 16. Relevant hormone gene expression and plasma hormone concentrations were assessed mainly at the end of 20 wk (Exp. 2).
RESULTS
In Exp. 1, Cy3G administration increased ileal but not colonic Gcg level by 2-fold (P < 0.05). In Exp. 2, Cy3G attenuated HFD-induced body-weight gain (20.3% at week 16), and improved glucose tolerance (26.5% at week 15) but not insulin tolerance. Although Cy3G had no effect on glucose tolerance in LFD mice, LFD/Cy3G/AB mice showed better glucose tolerance than LFD/Cy3G mice (23%). In contrast, HFD/Cy3G/AB mice showed worse glucose tolerance compared with HFD/Cy3G mice (15%). Beneficial effects of Cy3G in HFD mice were not associated with changes in plasma leptin, insulin or GLP-1 concentrations. However, Cy3G increased hepatic Fgf21 expression in mice in Exp. 1 by 4-fold and attenuated Fgf21 overexpression in HFD mice (Exp. 2, 22%), associated with increased expression of genes that encode FGFR1 and β-klotho (>3-fold, P < 0.05).
CONCLUSIONS
Dietary Cy3G may reduce body weight and exert metabolic homeostatic effects in mice via changes in hepatic FGF21.
背景
膳食多酚包括花色苷可作用于多个器官。
目的
我们旨在评估胰高血糖素样肽 1（GLP-1）、瘦素、胰岛素和成纤维细胞生长因子 21（FGF21）在介导纯化花色苷矢车菊素-3-葡萄糖苷（Cy3G）的代谢有益作用中的作用。
方法
在喂食低脂饮食（LFD；脂肪供能 10%）的 6 周龄雄性 C57BL-6J 小鼠中，评估肠道前胰高血糖素基因（Gcg；编码 GLP-1）和肝脏 Fgf21 的表达，单独或在饮用水中添加 1.6mg/L Cy3G 3 周[实验（Exp.）1；每组 n=5]。类似的小鼠喂食 LFD 或高脂肪饮食（HFD；脂肪供能 60%），同时添加或不添加 Cy3G 20 周。给予 Cy3G 的一半小鼠在第 11 至 14 周期间还在饮用水中添加了 4 种广谱抗生素（ABs），共分为 6 组（每组 n=8）。在第 2 至 16 周期间进行代谢耐量试验。主要在 20 周结束时评估相关激素基因表达和血浆激素浓度（Exp.2）。
结果
在 Exp.1 中，Cy3G 给药使回肠但不是结肠的 Gcg 水平增加了 2 倍（P<0.05）。在 Exp.2 中，Cy3G 减轻了 HFD 诱导的体重增加（第 16 周时增加 20.3%），改善了葡萄糖耐量（第 15 周时增加 26.5%）但不能改善胰岛素耐量。尽管 Cy3G 对 LFD 小鼠的葡萄糖耐量没有影响，但 LFD/Cy3G/AB 小鼠的葡萄糖耐量优于 LFD/Cy3G 小鼠（23%）。相反，HFD/Cy3G/AB 小鼠的葡萄糖耐量较 HFD/Cy3G 小鼠差（15%）。HFD 小鼠中 Cy3G 的有益作用与血浆瘦素、胰岛素或 GLP-1 浓度的变化无关。然而，Cy3G 在 Exp.1 中使小鼠肝脏 Fgf21 的表达增加了 4 倍，并减轻了 HFD 小鼠中 Fgf21 的过度表达（Exp.2，22%），与编码 FGFR1 和β-klotho 的基因表达增加（>3 倍，P<0.05）有关。
结论
膳食 Cy3G 可能通过改变肝脏 FGF21 来减少小鼠的体重并发挥代谢稳态作用。
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