EFFECTS OF PROLONGED ETHANOL INTAKE - PRODUCTION OF FATTY LIVER DESPITE ADEQUATE DIETS
EFFECTS OF PROLONGED ETHANOL INTAKE - PRODUCTION OF FATTY LIVER DESPITE ADEQUATE DIETS
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DOI：
10.1172/jci105200
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发表时间：
1965-01-01
影响因子：
15.9
通讯作者：
DECARLI, LM
中科院分区：
文献类型：
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作者：
LIEBER, CS;JONES, DP;DECARLI, LM
为了区分乙醇本身在酒精性脂肪肝发病机制中的作用与饮食缺陷的后遗症，在适当的饮食中施用乙醇。在 5 名受试者在代谢单位条件下进行的研究中，用乙醇等热量替代碳水化合物或在充足的饮食中添加乙醇会导致肝脏中脂肪堆积。这在老鼠身上得到了证实，通过在流质饮食中加入乙醇，克服了老鼠对酒精的天然厌恶。通过这种新的乙醇喂养技术，自发的乙醇摄入量几乎是传统喂养程序的两倍。与人类一样，用乙醇等热量替代蔗糖（占总热量的 36%）会产生脂肪水平，24 天后肝甘油三酯平均增加 8 倍。用脂肪等热量替代乙醇不会产生肝脏脂肪变性，这表明乙醇产生脂肪肝的能力大于脂肪本身。当对照饮食中省略蔗糖时，没有出现脂肪肝，这表明用乙醇观察到的脂肪变性不仅仅是由于缺乏碳水化合物热量造成的。喂食含乙醇饮食的大鼠总体体重增加量低于对照组，这表明乙醇对生长的支持效果不如蔗糖。据推测，乙醇产生的脂肪肝是由于乙醇对肝脏本身脂质代谢的直接影响，导致脂肪生成增加，内源性脂质和源自饮食的脂肪的氧化减少。
To differentiate the role of ethanol per se from sequelae of dietary deficiencies in the pathogenesis of the alcoholic fatty liver, ethanol was administered with adequate diets. In studies performed under metabolic unit conditions in 5 subjects, isocaloric substitution of carbohydrate by ethanol or addition of ethanol to an adequate diet resulted in fat accumulation in the liver. This was confirmed in rats whose natural aversion for alcohol was overcome by incorporating ethanol in a liquid diet. With this new ethanol feeding technique, the spontaneous ethanol intake was almost twice as high as with conventional feeding procedures. As in man, isocaloric replacement of sucrose (36% of total calories) by ethanol produced fatty lever, with an average 8 fold hepatic triglyceride increase after 24 days. Isocaloric replacement of ethanol by fat did not produce hepatic steatosis, demonstrating that the capacity of ethanol for generating fatty liver is greater than that of fat itself. No fatty liver developed when sucrose was omitted from the control diet, indicating that the steatosis observed with ethanol was not simply due to a lack of carbohydrate calories. Rats fed the ethanol-containing diet had less total body weight gain than the controls, indicating that ethanol supports growth less well than sucrose. It is postulated that the fatty liver produced by ethanol is due to direct effects of ethanol on lipid metabolism in the liver itself, with increased lipogenesis and decreased oxidation of endogenous lipids and fat originating from the diet.