Dietary olive oil intake induces female-specific hepatic lipid accumulation without metabolic impairment in mice

Olive oil is one of the most widely researched Mediterranean diet components in both ex- perimental models and clinical studies. However, the relationship between dietary olive oil intake and liver function in a healthy state of the body remains unclear. Because men are at a greater risk of developing hepatic diseases than women, and because hepatic metabolism is regulated by sex hormones, we hypothesized that olive oil-induced changes in hepatic metabolism would differ by sex. To test our hypothesis, 12-week-old C57BL/6JJcl male and female mice were fed an olive oil diet for 4 weeks. Blood was collected and serum biochemi- cal components were analyzed. Hepatic lipid accumulation was determined via histological analysis using Sudan III staining. Finally, transcript expression levels of hepatic metabolism- related genes were analyzed using quantitative polymerase chain reaction. We observed significant increased hepatic lipid droplet accumulation in olive oil-fed female mice. Serum biochemical and liver messenger RNA expression analyses revealed that the hepatic lipid accumulation was nonpathological and did not involve inflammation. Moreover, the ex- pression of genes related to triacylglycerol and fatty acid synthesis (Dgat1, Dgat2, Agpat3, and Fasn) was significantly upregulated in the liver of olive oil-fed female mice compared with control female mice. Our study demonstrates female-specific hepatic lipid accumula- tion without liver impairment in a dietary olive oil-fed mouse model. These findings provide a deeper mechanistic understanding of sex-dependent hepatic lipid metabolism of dietary oils.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )