Abstract
Liver steatosis can be induced by fasting or high-fat diet. We investigated by lipidomic analysis whether such metabolic states are reflected in the lipidome of hepatocyte lipid droplets (LDs) from mice fed normal chow diet (FED), fasted (FAS), or fed a high-fat diet (HFD). LC-MS/MS at levels of lipid species profiles and of lipid molecular species uncovered a FAS phenotype of LD enriched in triacylglycerol (TG) molecular species with very long-chain (VLC)-PUFA residues and an HFD phenotype with less unsaturated TG species in addition to characteristic lipid marker species. Nutritional stress did not result in dramatic structural alterations in diacylglycerol (DG) and phospholipid (PL) classes. Moreover, molecular species of bulk TG and of DG indicated concomitant de novo TG synthesis and lipase-catalyzed degradation to be active in LDs. DG species with VLC-PUFA residues would be preferred precursors for phosphatidylcholine (PC) species, the others for TG molecular species. In addition, molecular species of PL classes fitted the hepatocyte Kennedy and phosphatidylethanolamine methyltransferase pathways. We demonstrate that lipidomic analysis of LDs enables phenotyping of nutritional stress. TG species are best suited for such phenotyping, whereas structural analysis of TG, DG, and PL molecular species provides metabolic insights.
Highlights
Liver steatosis can be induced by fasting or highfat diet
A subsequent check by Western blotting of hepatocyte fractions demonstrated the exclusive presence of characteristic perilipin 2 in the lipid droplet (LD) fraction (Fig. 1C)
Significant differences were found for PL class composition in total PL extracted from LD and hepatocytes; in either case, PC class predominated (Table 2)
Summary
We investigated by lipidomic analysis whether such metabolic states are reflected in the lipidome of hepatocyte lipid droplets (LDs) from mice fed normal chow diet (FED), fasted (FAS), or fed a high-fat diet (HFD). Hepatic steatosis starts initially with accumulation of triacylglycerols (TGs) in hepatocytes This abnormal TG accumulation is due either to fasting or increased fat absorption [3], or to decreased hydrolysis [4, 5]. The decreased ratio of PC to phosphatidylethanolamine (PC/PE) can affect membrane integrity and leads to progression from steatosis into NASH [9]. Liver is one of the organs that have a division of cellular labor, of which hepatocytes constitute approximately 90% of total cell population These cells exhibit a high turnover of FAs and transiently store them in the form of TG in lipid droplets (LDs). No detailed studies on the LD lipidome of hepatocytes have been available
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