Alcohol consumption synergistically increases the risk and severity of liver damage in obese patients. To gain insight into cellular or molecular mechanisms underlying the development of fatty liver caused by ethanol-obesity synergism, we have carried out animal experiments that examine the effects of ethanol administration in genetically obese mice. Lean wild-type (WT) and obese (ob/ob) mice were subjected to ethanol feeding for 4 wk using a modified Lieber-DeCarli diet. After ethanol feeding, the ob/ob mice displayed much more pronounced changes in terms of liver steatosis and elevated plasma levels of alanine aminotransferase and aspartate aminotransferase, indicators of liver injury, compared with control mice. Mechanistic studies showed that ethanol feeding augmented the impairment of hepatic sirtuin 1 (SIRT1)-AMP-activated kinase (AMPK) signaling in the ob/ob mice. Moreover, the impairment of SIRT1-AMPK signaling was closely associated with altered hepatic functional activity of peroxisome proliferator-activated receptor γ coactivator-α and lipin-1, two vital downstream lipid regulators, which ultimately contributed to aggravated fatty liver observed in ethanol-fed ob/ob mice. Taken together, our novel findings suggest that ethanol administration to obese mice exacerbates fatty liver via impairment of the hepatic lipid metabolism pathways mediated largely by a central signaling system, the SIRT1-AMPK axis.

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Mounting interest in the potential value of nutritional therapy in the treatment of alcoholic liver disease (ALD) has arisen as a result of the growing body of evidence implicating nutritional intervention as a key player in ameliorating ALD. This review will focus on the involvement of nutrition in the pathogenesis of ALD, with extended focus on the role of micronutrients in the intervention or prevention of ALD. Oxidative damage is a major pathway in the initiation of ALD, and as such, many micronutrients have protective roles owing to their antioxidant properties. This can be either a direct action by scavenging free radicals or an indirect one elicited by increasing the synthesis or recycling of glutathione, the main intracellular antioxidant molecule. Micronutrients should be consumed as part of an energysufficient (at least 1400 kcal/day), macronutrient-based diet, as ALD progresses more quickly in people who have substituted a normal diet with alcohol, as opposed to those who drink alcohol in addition to their daily diet. Discontinuing alcohol consumption will enhance recovery, although this is not always possible with alcohol-addicted patients. In conclusion, an energy-sufficient diet high in vitamins and minerals will help protect against the formation and progression of ALD. However, alcohol abstinence is the recommended course of action to aid any recovery.

Teenage binge drinking is a major health issue; however, there is a paucity of data on liver injury. Herein, we investigated how acute ethanol affects juvenile hepatic cells through changes in oxidative stress, apoptosis, and liver function, as well as the ability of betaine, which can replen-ish the antioxidant glutathione and mitigate oxidative injury. Juvenile male Wistar rats were given either water or betaine (2% w/v) for 6 days and treated with either saline 0.15 mol/L NaCl or ethanol (75 mmol/kg bodyweight). After 24 h, liver enzymes, oxidative damage, apoptosis, and parameters of antioxidant enzyme activity were examined. Acute ethanol increased hepatic enzymes (99%, P < 0.05). Total protein and albumin levels were reduced by 14 and 18% (P < 0.001), respectively, which was prevented by betaine treatment. Cytosolic cytochrome c increased by 59% (P < 0.05), corresponding to a decrease in mitochondrial cytochrome c content, which was ameliorated with betaine. Cytosolic glutathione peroxidase was reduced with alcohol (P < 0.05) and was prevented with betaine. Subtle changes were observed in catalase, superoxide dismutase, glutathione reductase, and complex I activity after ethanol treatment. In summary, whilst juvenile animals appear to have higher basal levels of antioxidant enzymes, betaine conferred some protection against alcohol-induced oxidative stress.

Binge drinking is a major public health issue and ethanol-related liver insult may play a major role in the pathology of alcoholic liver disease. However, the degree of oxidative stress, cell death and contribution of acetaldehyde to liver damage over a 24-h period has yet to be determined. Herein, we aimed to investigate the effect of acute alcohol and elevated acetaldehyde levels on hepatic oxidative damage, apoptosis, and antioxidant enzyme activity over a 24-h period. Male Wistar rats were divided into four groups and animals were pre-injected (intraperitonially [i.p.]) with either saline (0.15 mol/L) or cyanamide (5-mmol/kg body weight), followed by either saline (0.15 mol/L) or ethanol (75-mmol/kg bodyweight). After 2.5, 6 and 24 h, hepatic cytosolic and mitochondrial fractions were analysed for indices of oxidative stress. At 2.5 h, cytosolic glutathione and malondialdehyde levels were significantly reduced and increased, respectively, with alcohol treatment. Caspase-3 activity and cytochrome c levels were increased with alcohol treatment at 24 h. The combination of cyanamide and alcohol treatment at 24 h led to a significant increase in serum alanine aminotransferase levels, and reduced albumin and total protein levels. Furthermore, glutathione peroxidase activity and glutathione reductase activity were significantly decreased and increased, respectively. Finally, superoxide dismutase activity was decreased in cytosol and increased in the mitochondria after cyanamide and ethanol treatment, respectively. This study indicates a complex differential effect of alcohol and acetaldehyde, whereby alcohol toxicity in the mitochondria takes place throughout the 24-h period, but raised acetaldehyde has a further detrimental effect on liver function.