Hepatic lipidomics reveal shifts in glycerolipid, phospholipid, and sphingolipid composition associated with hepatic fat accumulation in central bearded dragons (Pogona vitticeps)

Objective To characterize changes in the hepatic lipid profile and metabolic pathways associated with increasing hepatic fat accumulation in bearded dragons (Pogona vitticeps). Methods Untargeted lipidomic analysis was conducted using LC-MS-MS on liver samples from bearded dragons with varying hepatic fat content. Hepatic fat percentage was calculated from digital image analysis of scanned histopathology slides. After data normalization, associations between lipids and hepatic fat percentages were assessed using serial linear models adjusted for false discovery rate, volcano plots, and principal component analysis. Changes in fatty acyl chains of triacylglycerols and phospholipids were characterized graphically using bubble plots. Enrichment and pathway analyses were also performed to examine potential disruptions in lipid metabolic pathways. Results 36 central bearded dragons were sampled, and 976 lipid molecules were identified and quantified. Triacylglycerols were the most abundant and exhibited significant increases in concentrations and changes in fatty acyl chain charac-teristics with higher hepatic fat content. Notably, ether-linked glycerolipids were significantly enriched with increasing fat content. Phospholipids, especially phosphatidylethanolamines and phosphatidylinositols, demonstrated a negative association with hepatic fat accumulation, but fatty acyl chains remained stable. Sphingomyelins were also decreased with increasing hepatic fat. Conclusions This study shows some significant shifts in the hepatic lipidome of bearded dragons with increased hepatic fat, mainly involving glycerolipids, phospholipids, and sphingolipids. Clinical Relevance These findings reveal both shared and unique features when compared to mammalian and avian fatty liver disease and suggest species-specific lipid adaptive mechanisms.