Effect of long-term ethanol consumption and a high-fat diet on mitochondrial respiration in rat pancreatic acinar cells and hepatocytes

Chronic alcohol consumption may cause pancreatitis and alcohol-related liver diseases. Both adaptation and damage of liver mitochondria in animals on chronic ethanol and high-fat diets were demonstrated. It is currently not clear if ethanol or its metabolites such as fatty acid ethyl esters can cause mitochondrial damage to the pancreas. The present study aimed to evaluate the effect of chronic ethanol administration in combination with a high-fat diet on mitochondrial respiration in both pancreatic acinar cells and hepatocytes of rats. Wistar male rats on a high-fat diet (35% calories) were administered ethanol (6 g/kg body weight) by oral gavage for 14 days. Pancreatic acini cells and hepatocytes were isolated with collagenase digestion. The respiration of isolated cells was studied with a Clark electrode. Ethanol administration to rats kept on a high-fat diet was followed by a rapid loss of animal weight during the first 5 days of the experiment and diminished secretory response of pancreatic acini to acetylcholine, however, no changes in acinar cells ultrastructure, basal, oligomycin-insensitive or FCCP-uncoupled respiration were found. Meanwhile ethanol caused a significant (~40%) increase in basal and maximal FCCP-uncoupled respiration rate of isolated hepatocytes. In conclusion, chronic ethanol administration to rats on a high-fat diet does not cause mitochondrial damage in the pancreas, while mitochondria of the liver adapt to ethanol by increasing respiration rate. Keywords: ethanol, hepatocytes, high fat diet, mitochondrial respiration, pancreatic acinar cells