| 摘要: | 食源性糖化終產物(dietary advanced glycation end products, dAGEs)之生成主要來自梅納反應(Maillard reaction)。於食品中檢測具有代表性的dAGEs包含羧甲基賴胺酸(N?-carboxymethyllysine, CML)、羧乙基賴胺酸(N?-carboxyethyllysine, CEL)與甲基乙二醛-氫咪唑酮(methylglyoxal derived hydroimidazolone 1, MG-H1)。近來研究顯示飲食中的dAGEs攝入可能會導致促發炎反應並改變代謝產物及腸道菌群的組成，並與代謝症候群或慢性發炎具有正相關性。有鑑於此，本研究探討自由型態與蛋白質型態之CML於高脂高果糖飲食小鼠所造成之腦部功能障礙。在築巢試驗與水迷宮試驗中，研究結果顯示自由型態CML與含有蛋白質型態CML之BSA-CML與烘烤飼料具有惡化小鼠腦部認知障礙之趨勢，並發現小鼠大腦中不同種類AGEs的累積有顯著之改變，特別是餵食烘烤飼料之小鼠。進一步利用代謝體學分析腦部代謝物後，發現兩種型態之CML皆會顯著改變腦中代謝物之含量，特別是脂質代謝產物與胺基酸代謝物，進一步影響甘油脂與胺基酸代謝與生合成相關之代謝路徑。最後在腸道菌相之分析中，發現 CML、BSA-CML與烘烤飼料顯著改變小鼠腸道微生物之組成，特別是顯著降低能維持宿主健康之Lactobacillus 與Dubosiella_newyorkensis豐度。綜合以上之實驗結果，本研究發現自由型態與蛋白質型態之CML皆具有惡化高油脂飲食小鼠之大腦認知障礙之趨勢，此結果與攝食CML後顯著改變大腦中AGEs之積累、干擾腦部脂質與胺基酸代謝路徑與促進腸道微生物失衡具有高度相關性。
Dietary advanced glycation end products (dAGEs) found in food are primarily formed through the Maillard reaction. Representative dAGEs detected in foods include carboxymethyllysine (CML), carboxyethyllysine (CEL), and methylglyoxal-derived hydroimidazolone 1 (MG-H1). Recent studies have indicated that the dietary intake of dAGEs may induce pro-inflammatory responses, alter metabolite levels, and influence gut flora composition. Furthermore, it has been positively correlated with metabolic syndrome and chronic inflammation. In light of these findings, the present study sought to investigate the potential effects of free-type and protein-type CML on brain function in mice fed a high-fat and high-fructose diet. The results of the nesting and water maze tests indicated that free-form CML and BSA-CML, which contain protein-based CML, had a tendency to exacerbate cognitive deficits in mice. Furthermore, significant alterations in the accumulation of various types of AGEs were observed in the brains of mice consuming CML, particularly among those fed a baked diet. Following metabolomic analysis of brain metabolites, it was observed that both types of CML significantly altered levels of brain metabolites, particularly lipid and amino acid metabolites. These alterations subsequently affected metabolic pathways related to the metabolism and biosynthesis of glycerolipids and amino acids. Finally, analysis of the gut microbiota revealed that CML, BSA-CML, and the baked diet significantly altered the composition of intestinal microorganisms in mice. Specifically, these treatments led to a reduction in the abundance of beneficial bacteria such as Lactobacillus and Dubosiella_newyorkensis, which are known to play roles in maintaining host heatlh. Collectively, the present study demonstrated that both free and protein-bound CML tended to exacerbate cognitive deficits in the brain of mice fed a high-fat diet. These results were highly correlated with altered accumulation of AGEs in the brain, interference with lipid and amino acid biosynthesis and metabolism, and the promotion of dysbiosis. |
