Chronic Ethanol Consumption Lessens the Gain of Body Weight, Liver Triglycerides, and Diabetes in Obese ob/ob Mice

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 longterm drinking of light-to-moderate amounts of ethanol is safe for the liver.

Beneficial Effect of a Low Dose of Ethanol on Liver Function and Serum Urate in Rats Fed a High-Fat Diet

“…A recent study indicates the consumption of 1% ethanol in drinking water decreases risk factors for cardiovascular events in rats, such as serum cholesterol, triglyceride, and catecholamine metabolism in the peripheral system (6). Fromenty et al report glycemia and insulinemia in ob/ob mice are significantly reduced as a result of 1.5% ethanol in drinking water (7). These results suggest low doses of alcohol have protective effects against cardiovascular disease and diabetes.…”

Activation of peroxisome proliferator-activated receptor-γ by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice

“…Several reports have shown that ethanol feeding reduces the plasma adiponectin level in mice, rats, or micropigs (36,43,48). In contrast, some studies demonstrated that ethanol exposure increases the plasma adiponectin level in mice or patients with alcoholic hepatitis (5,11,44). Despite the controversial results, administration mouse recombinant adiponectin has been shown to attenuate alcohol-induced steatosis and inflammation (43).…”

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

“…7 To evaluate whether CCl 4 treatment could induce early apoptosis, the activity of caspases 2, 3, 8 and 9 was measured using the fluorescent ApoAlert Caspase Profiling Assay Plate (Clontech, Mountain View, CA) as described before. 18 A positive control (rat liver extract after ischemia reperfusion) was included in the assay and a specific inhibitor of each caspase was incubated with the protein extract to demonstrate the specificity of the signal.…”