Hepatic Lipidomics Unravels the Lipid-Lowering and Anti-Obesity Efficacy of Diacylglycerol Oil: Mechanistic Insights From High-Fat Diet-Induced Obese Mice

Abstract

This study employed a multidimensional approach combining clinical and animal experiments to elucidate the lipid-modulating mechanisms of diacylglycerol (DAG). In a 12-week intervention involving obese individuals, fasting serum triglyceride levels were significantly reduced in the DAG group compared to baseline. Within-group reductions in triglycerides and low-density lipoprotein (LDL) cholesterol were more pronounced in the DAG group than in the triacylglycerol (TAG) control group (p < 0.05). In a high-fat diet-induced obese mouse model, DAG significantly lowered serum total cholesterol, LDL levels, visceral fat weight (p < 0.05), attenuated hepatic steatosis, and altered hepatic lipid distribution. Lipidomic profiling revealed that DAG markedly downregulated hepatic triglycerides, ceramides, and monoacylglycerols, while normalizing sterol lipid levels. Pathway analyses based on differential lipids showed that DAG affected hepatic lipid composition mainly by intervening in the glycerophospholipid metabolism pathway. Mechanistically, DAG suppressed the expression of stearoyl-CoA desaturase 1 and fatty acid synthase, while upregulating carnitine palmitoyltransferase 1, thereby enhancing hepatic lipid metabolism through dual regulation: inhibition of synthesis and promotion of catabolism and oxidation. These findings reveal DAG's structure-dependent role in restoring lipid homeostasis and provide a theoretical foundation for functional lipid-based strategies targeting metabolic disorders.