Effects of ethanol ingestion and dietary fat levels on mitochondrial lipids in male and female rats

Abstract

The effects of sex, dietary fat levels, and ethanol ingestion on rat liver mitochondrial lipids have been studied. Two groups of male animals were fed either a low‐fat diet for about 76 days or a high‐fat diet for about 52 days, and two groups of female animals were fed the same low‐fat diet for about 50 days or the high‐fat diet for about 37 days. Ethanol was substituted isocalorically for carbohydrate and amounted to 36% of total calories. The total as well as individual concentrations of fatty acids, phospholipids, and neutral lipids were determined in all eight groups of animals. Variable changes were observed in the total fatty acid composition of mitochondria from each of the four groups of animals. After ethanol ingestion, there was a decrease in arachidonate/linoleate ratio in males, while no change was observed in females. Increasing the fat content of the diet decreased this ratio in both controls and experimentals, but it did not alter the effects of ethanol on either sex. Presumably, this was due to the fact that corn oil was the only source of lipid. After ethanol ingestion, the total fatty acid concentration increased in all groups of animals except the males fed the low‐fat diet. A decrease was observed in this group. The same pattern of change was reflected in changes in total phospholipid concentrations. In each case, the majority of the concentration change in total phospholipid could be accounted for by changes in phosphatidylcholine (PC). Measurement of choline oxidase (C.O.) showed that ethanol ingestion increased C.O. activity only in the low‐fat group of males. No change was observed in the other three groups. Chronic ethanol ingestion is known to increase the methylation of phosphatidylethanolamine (PE); therefore, in order to decrease PC, the increase in C.O. in the low‐fat males must have been of sufficient magnitude to offset the increase in PE methylation. Increasing the fat content of the diet offset the effect of ethanol on C.O. in males. Neither ethanol nor fat exerted much effect on C.O. in females. These results emphasize the importance of dietary levels of fat as well as sex in the study of liver mitochondria structure and function in relation to ethanol metabolism.

Selective reduction of delta 6 and delta 5 desaturase activities but not delta 9 desaturase in micropigs chronically fed ethanol.

“…This decrease in the ratio of 20:4w6 to linoleic acid (1 8:2w6) with ethanol was also observed in other studies with rats (3,4) and humans (5,6), although the effect of ethanol on fatty acid profile was variable among tissues and lipid fractions.…”

The glutathione precursor l-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat

“…The diet consisted of corn oil (37% of calories), protein (23%), carbohydrate, minerals, vitamins, and ethanol (ethanol diet) or isocaloric dextrin-maltose (control diet) supplemented with lipotropes. 12,13 OTC (a kind gift from Cynthia Leaf, Transcend Therapeutics) was added to the diet at a dose of 500 mg/kg/d. 10 The ethanol concentration ranged between 7% and 9% vol/vol depending on the demonstrated degree of intoxication and the urine alcohol concentration.…”

NADPH oxidase–derived free radicals are key oxidants in alcohol-induced liver disease

“…approximately 50/50 mixture of α-hydroxyethyl and lipid-derived free radical adducts (4,26). ESR studies of such systems using 13 C-ethanol have demonstrated the similarity of the hyperfine coupling constants and the presence of both radical adducts following chronic ethanol administration using Tsukamoto-French protocol (4). Spectrum II, with its unique β hydrogen hyperfine coupling of 3.2 G, is most likely the POBN/CO 2 • -free radical adduct formed by the abstraction of a hydrogen atom from endogenous formate to give CO 2 • -, which then reacts with POBN (27).…”