Long-Term Propolis Intake-Induced Liver Lipid Remodeling in Mice: Effects on Phospholipid-to-Glycerolipid Metabolism and Free Fatty Acid-Mediated Thermogenesis

Research on the patterns and mechanisms of liver lipid remodeling regulated by propolis is limited. In the present study, the nine-month experimental duration has shed light on the positive influences of propolis on lipid metabolism and thermogenesis capacity in the livers of mice. Eight major compounds in propolis were characterized using UPLC-QTOF-MS technology. Propolis significantly lowered serum triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C), but it also led to increased insulin (INS) levels. Lipidomics change trend analysis of 1671 lipid components across 42 categories revealed that the level of glycerophospholipids (GPs) decreased while glycerolipids (GLs) and fatty acids (FAs) increased in the liver. The expression levels of eight key genes involved in the conversion of GP to GL pathways in the liver were enhanced in the propolis group. Molecular docking results elucidated the high binding affinities between the eight components of propolis and eight receptors involved in lipid metabolism, indicating that primary compounds of propolis possess potent capabilities for phospholipid remodeling and lipolysis. These results imply that propolis could facilitate the browning of the liver adipose tissue, promote the conversion of GPs to DGs and FFAs, enhance the consumption of FFAs through thermogenic pathways, and thereby exert lipolytic and hepatoprotective functions.