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|標題:||Development of special fatty acid composition formulas for improving vitamin B6 status|
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|摘要:||維生素B6是水溶性維生素，其活化型磷酸比哆醛 (pyridoxal phosphate, PLP) 在體內參與百種酵素反應包含胺基酸、神經傳遞、核酸、血紅素和脂質等代謝。脂肪酸的組成在生物體細胞膜結構以及能量代謝與儲存中扮演重要角色。異常的脂肪酸分布與許多病理狀態有關，如自體免疫疾病、心血管疾病和糖尿病等。已知較低的血漿活化型磷酸比哆醛濃度是獨立的心血管疾病的危險因子，而提升維生素B6有助於預防心血管疾病，因此維持健康人體內維生素B6濃度有其重要性及生理意義。許多文獻指出攝取富含n-3脂肪酸的魚油有效降低罹患心血管疾病風險，並助於動物後肢缺血模式之恢復後血流，因此無論是調節脂肪酸比例或是增進維生素B6活化型磷酸比哆醛濃度，都對健康人的心血管疾病預防有很大助益。過去雖曾有研究指出維生素B6不足影響體內n-6脂肪酸和n-3脂肪酸的比例，然至今並無任何文獻探究飲食中不同比例脂肪酸如何影響體內維生素B6代謝。本論文是第一個系統性探討飲食配方中不同脂肪酸組成對維生素B6代謝之影響的研究。根據過去本研究室未發表的體外先期研究 (in vitro pilot study) 曾發現特定的脂肪酸會促進維生素B6磷酸化，促進維生素B6活化，也發現特定脂肪酸會抑制維生素B6去磷酸化，進而影響胞內不同形式的維生素B6比例，而特定脂肪酸對重要的維生素B6代謝酵素活性有不同影響。我們因此針對如何有效提升維生素B6活化減少維生素B6降解設計出不同脂肪酸組合之飲食配方，並在小鼠模式中測試不同配方對於體內脂肪酸分佈以及體內維生素B6代謝之影響。實驗結果發現不同油組成的飲食配方對於小鼠維生素B6代謝有不同程度的顯著影響，進一步探討維生素B6與特定其之間的相關性係與可能機制，找出對於維生素B6代謝較為有利的脂肪酸配方組成。本論文是第一個發現特定脂肪酸組成有助於提升維生素B6有研究。|
Vitamin B6 is a water-soluble essential nutrient and functions as a coenzyme in 100 enzymatic reactions involved in the metabolism. Vitamin B6 exists as pyridoxal (PL), pyridoxal 5'-phosphate (PLP) as its major bioactive form (Midttun et al., 2007). Low plasma PLP concentrations are independent risk factors for cardiovascular disease, and severe vitamin B-6 deficiency has been associated with altered n-6 and n-3 fatty acid profiles in plasma and tissue lipids (Zhao et al., 2012a). Fatty acids play an important role in the composition of cell membranes and the energy metabolism. Abnormal plasma fatty acid profile is associated with many pathological conditions such as autoimmune disease, cardiovascular disease, and diabetes (Fraser et al., 1999), (Leaf, 2001), (Tiemeier et al., 2003). However, the impact of various dietary fatty acid consumptions on vitamin B6 metabolism has never been investigated before. Our study is the first study reporting that supplementation with new fatty acid formulas on vitamin B6 in vivo. In our pilot in vitro study, and we found that specific fatty acids could alter vitamin B6 metabolism. Therefore, we established different fatty acids formulas to search the most efficient improvement of vitamin B6 in vivo. In our in vitro model, we treated human erythrocytes with different fatty acids and investigated vitamin B6 metabolic enzymes as well as B6 vitamer profile. Three independent in vivo models were used. In the 1st study twelve healthy C57BL/6J mice received either 10% oil rich in omega-3 fatty acid, or 10% soybean oil rich in omega-6 fatty acid for 27 weeks. In the 2nd and 3rd studies, twenty-eight and twenty-nine female C57BL/6J mice were gavaged a PUFA enriched diet containing different omega-3 fatty acids formulas for 21 days. Fatty acid composition was determined by GC-FID. In our study, we found that various dietary fatty acid consumptions had different impacts on vitamin B6 metabolism. We study the relationships among B6 vitamers and fatty acid composition and further explored the potential mechanisms by which specific fatty acid alters vitamin B6 metabolism.
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