| 摘要: | 飲食中的糖化終產物 (dietary advanced glycation end products, dAGEs) 主要源自於梅納反應。具代表性之 dAGEs 如羧甲基賴胺酸 (Nε-carboxymethyllysine, CML) 、羧乙基賴胺酸 (Nε-carboxyethyllysine, CEL) 及甲基乙二醛-氫咪唑酮 (methylglyoxal derived hydroimidazolone, MG-H1)。近來有研究顯示 dAGEs 的攝取可能會導致體內代謝產物以及腸道菌相之改變，且 dAGEs 的攝入與許多代謝慢性疾病具有正相關性。有鑑於此，本研究利用代謝體學探討 dAGEs對於高脂高果糖飲食誘發小鼠肥胖過程中所造成之健康影響。本研究首次證明給予 CEL 和 MG-H1 會顯著降低高脂高果糖飲食小鼠的體重，但給予加熱飼料會導致高脂高果糖飲食小鼠體重顯著的增加。血清生化分析的結果顯示，與高脂高果糖飲食組相比，給予 dAGEs 會明顯增加 LDL/HDL 比值。在代謝體學分析之結果顯示，給予 MG-H1 以及加熱飼料會導致高油脂飲食小鼠體內代謝產物異常，特別是脂質代謝產物。在腸道菌代謝物結果中，發現dAGEs顯著提升次級膽汁酸之合成，特別是給予MG-H1。另一方面，腸道菌相的結果顯示，dAGEs 會改變厚壁菌門與擬桿菌門的比值，進而導致體內腸道健康失衡。在相關性分析結果中，發現小鼠體內 AGEs與Bacteroidetes呈現負相關性；而與Faecalibaculum呈現正相關性，同時 Faecalibaculum 也與次級膽汁酸以及血脂指標物質呈現正相關性。綜合以上實驗結果，本研究證實飲食中的 dAGEs 會對於肥胖小鼠健康造成不良影響，特別是干擾體內脂質代謝，此不良影響與腸道菌相之改變有關。
Dietary advanced glycation end products (dAGEs) are primarily derived from the Maillard reaction, a series of reactions between reducing sugars and proteins. Representative dAGEs include Nε-carboxymethyllysine (CML), Nε-carboxyethyllysine (CEL), and methylglyoxal-derived hydroimidazolone (MG-H1). Recent studies have shown that the consumption of dAGEs significantly alters metabolite formation and composition of gut microbiota. Meanwhile, research has shown a positive correlation between dAGE intake and various metabolic chronic diseases. Therefore, this study aims to investigate the effects of dAGEs on mice fed a high-fat and high-fructose diet using metabolomics. The results showed that administration of CEL and MG-H1 significantly reduced the body weight of mice fed with a high-fat and high-fructose diet, while supplementation of a heated diet resulted in a significant increase in body weight. Furthermore, serum biochemical analysis results showed that administration of dAGEs significantly increased the LDL/HDL ratio compared to the high-fat and high-fructose diet group. In metabolomics, the administration of MG-H1 and a heated diet significantly altered the composition of liver metabolites, particularly lipid metabolites, in mice fed a high-fat and high-fructose diet. Meanwhile, dAGEs significantly increased the formation of secondary bile acids, particularly supplementation with MG-H1. Importantly, gut microbiota results showed that dAGEs profoundly altered the ratio of Firmicutes to Bacteroidetes, resulting in gut microbiota dysbiosis. Correlation analysis revealed that AGEs were negatively associated with the abundance of Bacteroidetes, while AGEs had a positive relationship with the abundance of Faecalibaculum. Also, the abundance of Faecalibaculum was positively correlated with secondary bile acids and blood lipid parameters. Altogether, this study demonstrates for the first time that dAGEs adversely impact the health of mice with obesity, particularly disturbing lipid metabolism. These adverse effects caused by dAGEs were, at least in part, due to gut microbiota dysbiosis. |
