Hepatic Lipidomics Analysis Reveals the Antiobesity and Cholesterol-Lowering Effects of Tangeretin in High-Fat Diet-Fed Rats

Tangeretin
(TAN) exhibited antilipogenic, antidiabetic, and lipid-lowering
effects. However, the lipid biomarkers and the underlying mechanisms
for antiobesity and cholesterol-lowering effects of TAN have not been
sufficiently investigated. Herein, we integrated biochemical analysis
with lipidomics to elucidate its efficacy and mechanisms in high-fat
diet-fed rats. TAN at supplementation levels of 0.04 and 0.08% not
only significantly decreased body weight gain, serum total cholesterol,
and low-density lipoprotein cholesterol levels but also ameliorated
hepatic steatosis. These beneficial effects were associated with the
declining levels of fatty acids, diacylglycerols (DGs), triacylglycerols,
ceramides, and cholesteryl esters by hepatic lipidomics analysis,
which were attributed to downregulating lipogenesis-related genes
and upregulating lipid oxidation- and bile acid biosynthesis-related
genes. Additionally, 21 lipids were identified as potential lipid
biomarkers, such as DGs and phosphatidylethanolamines. These findings
indicated that the modulation of lipid homeostasis might be the key
pathways for the mechanisms of TAN in the antiobesity and cholesterol-lowering
effects.