Gender Differences in the Response of Hepatic Fatty Acids and Cytosolic Fatty Acid-Binding Capacity to Alcohol Consumption in Rats

Abstract

To investigate possible gender differences in the response of hepatic fatty acids and cytosolic fatty acid-binding capacity to ethanol consumption, both female and male rats (41 days of age) were pair fed liquid diets (with a littermate of the same sex) for 28 days. The diets contained 36% of energy either as ethanol or as additional carbohydrate. After ethanol feeding, the hepatic concentration of fatty acids increased 155% in females (P less than 0.01), whereas there was only a trend for an increase (22%) in males. This was associated with a much smaller increase of cytosolic fatty acid-binding capacity in females (58%) than in males (161%). Whereas the ethanol-induced increase in fatty acid-binding capacity provided an ample excess of binding sites for the fatty acids in males, the increase in females was barely sufficient for the binding of the large increase of fatty acids produced by ethanol in the females. The cytosolic protein responsible for this binding, the liver fatty acid-binding protein of the cytosol (L-FABPc), also promotes esterification of the fatty acids. In keeping with the postulated role of this protein, the ethanol-induced increases in hepatic triacylglycerols, phospholipids, and cholesterol esters were smaller in females than in males. The gender difference in cholesterol esters was associated with parallel changes in acyl-CoA transferase activity. A possible implication of the relatively small and most likely inadequate increase in liver fatty acid-binding capacity and fatty acid esterification during alcohol consumption in the females is that under these circumstances the risk for development of a potentially deleterious accumulation of fatty acids in the liver is increased, thereby contributing to the enhanced vulnerability of females to alcohol-induced hepatotoxicity.

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

“…20 Animal experiments of chronic alcohol consumption have demonstrated that females tend to accumulate more fatty acid within the liver than males. 21 This observation in animals corroborates prospective studies demonstrating the greater likelihood of liver disease in women after consuming less ethanol and within a shorter time period compared to men. 22 Despite the increased recognition of sex differences that can occur after chronic alcohol consumption, few investigations have examined the interaction of chronic alcohol consumption and gender in affecting HGN capacity and blood glucose homeostasis.…”

“…In support, we observed an elevated triglyceride content in the livers from ethanol fed males compared to ethanol fed females, whereas an elevated accumulation of fat has previously been reported in chronic ethanol fed females compared to males. 21 We have no explanation for the discrepancy, but we note two distinct differences between the studies that could support our contention pertaining to the length of chronic alcohol consumption and the fat content within the diet. Specifically, we examined animals chronically fed an ethanol diet for 8 weeks, whereas others 21 examined the impact of alcohol consumption after 4 weeks.…”

Hepatocyte Retinoid X Receptor α-Dependent Regulation of Lipid Homeostasis and Inflammatory Cytokine Expression Contributes to Alcohol-Induced Liver Injury

“…L-FABP, a PPAR␣ target-gene, binds fatty acids and stimulates their esterification, thereby attenuating fatty acid accumulation and toxicity (Shevchuk et al, 1991;Lieber, 2004). Chronic ethanol ingestion increases the concentration of L-FABP in the liver (Shevchuk et al, 1991;Lieber, 2004).…”

“…Chronic ethanol ingestion increases the concentration of L-FABP in the liver (Shevchuk et al, 1991;Lieber, 2004). The levels of L-FABP mRNA were quantified in ethanol treated wild-type and hepatocyte RXR␣-deficient mice (Fig.…”

Recent insights into the biological functions of liver fatty acid binding protein 1

“…A high-carbohydrate diet increases FABP1 content in the liver and intestine ( 37 ). Low dose chronic alcohol consumption induces a marked increase of FABP1 in the livers of rats ( 38,39 ). Methionine/ choline-defi cient diets decreased FABP1 signifi cantly in a rat model of nonalcoholic steatohepatitis (NASH) ( 40 ), while dexamethasone has been reported to downregulate FABP1 by an indirect endocrine effect ( 41 ).…”