Roles of Hormonal and Nutritional Factors in the Regulation of Rat Liver Alcohol Dehydrogenase Activity and Ethanol Elimination Rate in Vivo

Abstract

Fasting reduced the liver alcohol dehydrogenase (ADH) activity by 51% (p less than 0.001). Insulin, within 2 hr, increased the ADH activity found in fasted animals by 28% (p less than 0.02). Insulin administration failed to stimulate the reduced ADH activity in diabetic rats. However, ADH activity in the diabetic-fed rats decreased by 52-54% (p less than 0.001) compared to normal-fed rats regardless of whether they were meal-fed or refed the normal chow. Glucagon blocked by 15% (p less than 0.02) the increase in ADH activity associated with refeeding. Furthermore, insulin caused a marginal stimulation of ethanol elimination rate (EER) when administered to fasted rats. All these results imply that insulin and glucagon may not be the only determining factors in the control of liver ADH activity associated with fasting and refeeding. Meal-feeding or refeeding a high carbohydrate fat-free diet compared to the normal chow-diet caused 29% (p less than 0.001) and 36% (p less than 0.05) decreases in ADH activity, respectively. Concomitant decreases in EER caused by high carbohydrate fat-free diet feeding were also observed under identical conditions. These results raise the possibility that the amount and the type of carbohydrate may be crucial in the regulation of ADH and EER. Alternatively, the presence of fat may be important in maintaining the normal level of ADH and EER.

Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease

“…It further was shown in in-vitro studies that the activity of ADH may, at least in part, be regulated through growth hormones like insulin-like growth factor I and insulin-dependent signalling pathways 32–34. In the studies of Lakshman et al ,34 it was further shown that feeding a high carbohydrate, fat-free diet compared with a normal chow diet caused a marked decrease in ADH activity. Furthermore, in diabetic rats, ADH activity was found to be reduced by approximately 53% when compared with control animals 34.…”

“…In the studies of Lakshman et al ,34 it was further shown that feeding a high carbohydrate, fat-free diet compared with a normal chow diet caused a marked decrease in ADH activity. Furthermore, in diabetic rats, ADH activity was found to be reduced by approximately 53% when compared with control animals 34. In the present study, fasting blood ethanol levels of children were strongly associated with markers of insulin resistance (eg, HOMA-IR, leptin, TG levels) and liver damage (eg, ALT levels) suggesting that alterations in insulin signalling (eg, beginning insulin resistance) may contribute to the increased ethanol levels found in fasting plasma of children suffering from early signs of NAFLD.…”

ADH1B∗2 Is Associated With Reduced Severity of Nonalcoholic Fatty Liver Disease in Adults, Independent of Alcohol Consumption

“…29,30 In addition to increased obesity-related production of ethanol, other hypotheses suggest that modifications in insulin signaling followed by decreased ADH activity in the liver or adipose tissue could be responsible for an impaired ethanol metabolism. 31,32 In this regard, earlier studies conducted in rats suggest that the activity of ADH is significantly reduced by high-carbohydrate, fat-free diet feeding compared with a normal chow diet. Furthermore, in diabetic rats, ADH activity is found to be reduced by approximately 53% when compared with control animals.…”

“…Furthermore, in diabetic rats, ADH activity is found to be reduced by approximately 53% when compared with control animals. 31 The overproduction of endogenous ethanol along with impairments in insulin signaling in obese and diabetic patients may alter ADH activity in the liver, subsequently leading to an impaired ethanol metabolism and elevated blood ethanol levels in patients with NAFLD. The increased production of microbiota-related ethanol may result in up-regulation of activity of the enzyme cytochrome P450 2E1, which catalyzes the oxidation of ethanol but produces free radicals favoring oxidative damage, mitochondrial dysfunction, and liver inflammation.…”

Effects of thyroxine on the expression of alcohol dehydrogenase in rat liver and kidney

“…growth hormone (51, androgens (61, insulin and glucagon (7,8) and thyroid hormone. Previous studies have shown that thyroidectomy or propylthiouracil treatment increases liver ADH activity, whereas thyroid hormone administration reduces activity in thyroidectomized or control rats (9-13).…”