High-fat diet supplemented with soybean diacylglycerol oil protects liver homeostasis <i>via</i> maintaining endoplasmic reticulum function in C57BL/6J mice

Diacylglycerol-rich edible oil can prevent obesity-induced hyperlipidaemia in both animals and humans, while the effect of diacylglycerol-rich oil diets on liver function remains poorly understood. Therefore, male C57BL/6J mice were separately fed with different meals, including 7% (w/w) soybean triacylglycerol oil, 25% (w/w) soybean triacylglycerol oil or 25% (w/w) soybean diacylglycerol oil for 12 weeks. A soybean diacylglycerol oil-based high-fat diet preserved plasma lipid levels and liver function, whereas a soybean triacylglycerol oil-based high-fat diet caused elevated levels of plasma lipids and excess hepatic fat deposition. Endoplasmic reticulum dysfunction is a marker reflecting aggravated hepatic disorders and hyperlipidaemia. Transcriptome sequencing revealed that the soybean diacylglycerol oil-based high-fat diet maintained the expression of several key genes in endoplasmic reticulum function. The results of serum lipidomic profiles showed that the soybean diacylglycerol oil-based high-fat diet caused less hepatoxic lipid metabolites such as lysophosphatidylcholine that drives liver damage <i>via</i> triggering endoplasmic reticulum stress. Our findings imply that replacing triacylglycerol with diacylglycerol in a high-fat diet can protect liver homeostasis by maintaining endoplasmic reticulum function caused by inhibiting an increase in lysophosphatidylcholine.