Date of Award
Doctor of Philosophy
Dileep S. Sachan
Jack S. Ellison, Naima Moustaid Moussa, Jay Whelan
The effects of saturated fatty acids (SFA), cis fatty acids (CFA), and trans fatty acid (TFA) on blood ethanol clearance were determined in 5-week-old male Sprague-Dawley rats. In the first phase, it was established that the blood ethanol concentrations (BEC) of the SFA and CFA groups were higher than those of the TFA group after 2 weeks of dietary treatment. While the concentrations of liver triglyceride were significantly lower in the TFA group, the levels of plasma triglyceride were not affected by the types of dietary fatty acids.
Possible mechanisms of dietary fat related changes on BEC were investigated in these rats. It was found that TFA enhanced blood ethanol clearance in comparison to SFA or CFA; however, the hepatic alcohol dehydrogenase activity was not affected after either 2 or 6 weeks of dietary treatment. The activity of carnitine palmitoyl transferase-I was also not affected by the types of dietary fatty acid. The excretion of ethanol in urine was higher in the TFA group than in the CFA group during the first 4 hours post- ethanol administration and might partially explain the dietary fatty acids related changes in BEC. In addition, the concentrations of acylcarnitine were changed parallel with BEC of the dietary groups. Thus, the reduction in BEC in rats fed the TFA may be at least in part mediated through parallel changes in carnitine concentrations.
Differences in ethanol uptake and metabolism were examined in small intestines of rats fed dietary SFA, CFA, or TFA. The uptake and/or metabolism of ethanol was measured in everted intestinal sacs. Ethanol transport expressed as the ratio of serosal to mucosal ethanol concentrations and the in vitro absorption rate of ethanol was not significantly affected by dietary fatty acids. However, when the amount of ethanol metabolized to CO2 during the transport process was taken into account, uptake and metabolism of ethanol by the proximal segments of the small intestine were significantly higher in the rats fed TFA and CFA than in those fed SFA. Because ethanol oxidation was not significantly different between the CFA and TFA group, some other mechanism must be responsible for the differences in BEC of CFA and TFA animals. Nonetheless, it is noted that ethanol metabolism in extrahepatic tissues can not be ignored for the effects of SFA and unsaturated fatty acids on ethanol pharmacokinetics.
The fatty acid composition data revealed that the fatty acid profiles of diets were reflected in the fatty acid content of various tissues. The phospholipids fraction of the liver and small intestine of rats fed the TFA diet for 6 weeks had a higher percentage of linoleic acid and lower percentages of palmitic, stearic, and arachidonic acids than those fed the SFA and CFA diets. Compared with rats fed the CFA diet, the fatty acid composition in the liver microsomes of those fed the TFA diet was characterized by a significant decrease in palmitic, stearic, and oleic acids and an increase in linoleic acid. These fatty acid changes were similar in plasma. The fatty acid composition data supports the suggestion that elaidic acid interfered with the conversion of linoleic acid to arachidonic acid which has been shown to protect liver from alcohol-induced injury.
Mong, Mei-Shin, "Effects of Cis and Trans Unsaturated Fatty Acids on Blood Ethanol Clearance in Rats. " PhD diss., University of Tennessee, 1999.