A lipidomics approach identifies the lipid classes modulated in response to hepatic steatosis in obese fa/fa rats relative to lean Zucker rats.

Mass spectrometry-based lipidomics analysis of liver tissues from obese fa/fa and lean Zucker rats (n = 8/group) was carried out. Hepatic steatosis, the accumulation of >5% lipid (w/w) in liver due to obesity forms the physiological context of this study, and differences in the lipid profile of steatotic and healthy livers are expected to provide insight into how lipid metabolic processes respond to obesity. A total of 1000 lipids within 21 different classes of lipids were identified using an iterative auto-MSMS analyses of all liver tissues combined. Among these, 175 lipids were significantly affected when the lipidome of the two rat groups was compared (T-test, P < 0.05). They include PC, PE, PS, PI, PA, PG, lyso-PC and lyso-PE which constituted >50% of all significant changes (P < 0.05) observed among all detected lipids. >100 of these lipids had Log2 Fold change (Log FC) values of >5 when the two rat groups were compared. PE had the highest FC increase in obese liver tissues while PG and PC had the highest FC increase in lean rat liver tissues. Volcano plots of significant lipids (unpaired T-Test for Obese vs. Lean rats, P ≤ 0.05) showed upregulation of 99 and 76 lipids in ESI positive and ESI negative modes, respectively. These results showed a major change in the lipidome profile, and particularly the lipid classes of the rat liver of obese fa/fa rats with implications for changes in overall lipid metabolism due to obesity and hepatic steatosis.