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长期摄入乙醇可减轻肥胖的ob/ob小鼠的体重增加、肝脏甘油三酯水平并改善糖尿病状况。

Chronic ethanol consumption lessens the gain of body weight, liver triglycerides, and diabetes in obese ob/ob mice.

作者信息

Fromenty Bernard, Vadrot Nathalie, Massart Julie, Turlin Bruno, Barri-Ova Nadège, Lettéron Philippe, Fautrel Alain, Robin Marie-Anne

机构信息

Institut National de la Santé et de la Recherche Médicale, Rennes, France.

出版信息

J Pharmacol Exp Ther. 2009 Oct;331(1):23-34. doi: 10.1124/jpet.109.155168. Epub 2009 Jul 8.

Abstract

Clinical studies suggest that moderate alcohol consumption can have beneficial effects, in particular regarding cardiovascular events, insulin resistance, and type 2 diabetes. In this study, lean and obese diabetic ob/ob mice were submitted or not to chronic ethanol intake via the drinking water for 6 months, which was associated with moderate levels of plasma ethanol. Plasma levels of alanine aminotransferase and aspartate aminotransferase were not increased by alcohol intake. Ethanol consumption progressively reduced the gain of body weight in ob/ob mice, but not in lean mice, and this was observed despite higher calorie intake. Increased plasma free fatty acids and glycerol in ethanol-treated ob/ob mice suggested peripheral lipolysis. Glycemia and insulinemia were significantly reduced, whereas adiponectinemia was increased in ethanol-treated ob/ob mice. Liver weight and triglycerides were significantly decreased in ethanol-treated ob/ob mice, and this was associated with less microvesicular steatosis. Hepatic levels of AMP-activated protein kinase and the phosphorylated form of acetyl-CoA carboxylase were higher in ethanol-treated ob/ob mice, suggesting better fatty acid oxidation. However, hepatic mRNA expression of several lipogenic genes was not reduced by ethanol consumption. Finally, mild oxidative stress was noticed in the liver of ethanol-treated mice, regardless of their genotype. Hence, our data are in keeping with clinical studies suggesting that moderate ethanol intake can have beneficial effects on type 2 diabetes and insulin sensitivity, at least in part through increased levels of plasma adiponectin. However, further studies are needed to determine whether long-term drinking of light-to-moderate amounts of ethanol is safe for the liver.

摘要

临床研究表明,适度饮酒可能具有有益作用,特别是在心血管事件、胰岛素抵抗和2型糖尿病方面。在本研究中,将瘦型和肥胖型糖尿病ob/ob小鼠通过饮用水给予或不给予慢性乙醇摄入6个月,这与中等水平的血浆乙醇相关。饮酒并未增加血浆丙氨酸转氨酶和天冬氨酸转氨酶水平。乙醇摄入使ob/ob小鼠的体重增加逐渐减少,但对瘦型小鼠没有影响,尽管热量摄入较高,但仍观察到这种情况。乙醇处理的ob/ob小鼠血浆游离脂肪酸和甘油增加表明外周脂肪分解。乙醇处理的ob/ob小鼠血糖和胰岛素血症显著降低,而脂联素血症增加。乙醇处理的ob/ob小鼠肝脏重量和甘油三酯显著降低,这与较少的微泡性脂肪变性相关。乙醇处理的ob/ob小鼠肝脏中AMP活化蛋白激酶和乙酰辅酶A羧化酶的磷酸化形式水平较高,表明脂肪酸氧化更好。然而,乙醇摄入并未降低几种脂肪生成基因的肝脏mRNA表达。最后,无论基因型如何,在乙醇处理小鼠的肝脏中均观察到轻度氧化应激。因此,我们的数据与临床研究一致,表明适度乙醇摄入至少部分通过增加血浆脂联素水平对2型糖尿病和胰岛素敏感性具有有益作用。然而,需要进一步研究以确定长期饮用少量至中等量乙醇对肝脏是否安全。

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