飲食與代謝記憶：嬰幼期的營養修飾對成熟期脂質及脂蛋白代謝之影響

DIET AND METABOLIC MEMORY IN RATS: INFLUENCE OF EARLY NUTRITIONAL MANIPULATIONS ON LIPID AND LIPOROTEIN METABOLISM IN LATER LIFE

高血膽固醇症是引起動脈硬化症的原因之一。動脈硬化症乃溯自嬰幼期，而進展於其後數十年的生命裡。因此，有必要研究嬰幼期的膳食與成年後對膽固醇食物的反應之間的關係。為探討飲食與代謝記憶（或稱為膽固醇代謝的蓋印效果（imprinting effect））的關係，利用大白鼠做動物實驗，得到以下的結果：首先，探討成長中大白鼠的血脂質、脂蛋白及輔蛋白之變化特性；由出生直後到斷奶期（出生後2～3星期）脂蛋白的變化非常急劇，但這種顯著變化在斷奶後期及成年期並沒有發現。又，哺乳期及斷奶直後的營養干預對血脂質及脂蛋白影響甚巨。嬰幼期給予降膽固醇的膳食條件（水易溶性膳食纖維、Cholestyramine、植物油）於成年期反而導致高血膽固醇症的反應。早期的膽固醇攝取會減少成年期的膽固醇血症的反應，同時經由灌流肝臟得知抑制低密度脂蛋白的分泌。以上結果顯示嬰幼期膽固醇恆常性的蓋印效果發現在成年期有所謂代謝記憶的存在，此種記憶效果推定是由於肝臟脂蛋白的分泌及隨後的分解代謝所引起。

Hypercholesterolemia is considered to be one of the leading causes of atherosclerosis. The disease begins in childhood and progresses over sereral decades in later life. Therefore, it is quite important to examine the relationship between the diet in early life and the cholesterolemic response in later life. In order to get a possible relationship between diets and metabolic memory so called an imprinting effect on cholesterol metabolism, a series of experiments were carried out using rats as an animal model. The results obtained are as follows. First, the ontogenic development of serum lipids, lipoproteins and apolipoproteins was characterized. The results clearly indicated that metabolism of serum lipoproteins changes quite rapidly from the postnatal day to around the weaning periods (2 to 3 weeks after birth). However, such a marked change was not observed during the growing period (or late weaning period) and adulthood as well. In addition, nutritional intervention markedlyinfluenced serum lipid and lipoprotein profiles during the suckling and postweaning period. Hypocholesterolemic dietary condition (water solule dietary fiber, choloestyramine and vegetable oil) in early life resulted in hypercholesterolemic response in later life. Cholesterol feeding in early life reduced the serum cholesterolemic response and specifically suppressed the secretion of low density lipoprotein in adult life by the perfused liver when challenged with cholesterol diet. These results strongly suggest that imprinting effect of cholesterol homeostasis in early life is expressed, as 'metabolic memory' in later life. The secretion of lipoprotein-cholesterol from the liver and its subsequent catabolism appeared to be responsible for the expression of the memory effect.