Moderate alcohol consumption down-regulates 11I²-hydroxysteriod dehydrogenase type-1 (11I²-HSD1) in the liver of high-fat-diet fed rats

Abstract

Obesity is one of the leading cause metabolic disorders in the western-industrialised countries. Metabolic disorders such as obesity, insulin resistance and non-alcoholic fatty liver disease is caused by the high-fat-diet intake in those population. The excess fat accumulation in the body causes alterations in various metabolic pathways, one of which is the conversion active glucocorticoids to inactive glucocorticoids. Although there are several studies that convey the effect of heavy alcohol consumption is linked with the pathogenesis of metabolic disorders and alcoholic fatty liver disease, the effect of light-to-moderate alcohol consumption is largely unknown. A number of epidemiological studies has demonstrated that regular light-moderate alcohol consumption lowers the risk of life threatening diseases such as cardiovascular disease and non-alcoholic fatty liver disease (NAFLD). Thus, in this study we investigated the effect of chronic light-to-moderate alcohol consumption in high-fat diet-fed rats on the hepatic regulation of 11I²-HSD1 protein expression and its enzyme activity together with measurements of serum and hepatic corticosterone levels. The results demonstrated that light-to-moderate alcohol consumption down-regulated the expression of 11I²-HSD1 protein in the liver together with decreased enzyme activity. In parallel, light-to-moderate alcohol also lowered the serum and liver corticosterone levels in rats fed with high fat diet. In conclusion, the present study demonstrated that chronic light-moderate alcohol consumption down-regulated 11I²-HSD1 protein expression and decreased enzymatic activity in the liver of HFD-fed rats, which was associated with a reduction in circulating and liver corticosterone levels. Thus, the present study provides mechanistic evidence for the earlier epidemiological studies that indicate light-to-moderate alcohol consumption lowers the risk of development of metabolic syndrome leading to NAFLD, at least in part, via targeting 11I²-HSD1.

Date of Award	2018
Original language	English