Cosupplementation with DHA and medium‐chain triglycerides ameliorates NAFLD and reduces amyloid‐β accumulation by modulating hepatic lipid metabolism in APP/PS1 mice

Abstract Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is associated with Alzheimer's disease (AD). Both docosahexaenoic acid (DHA) and medium chain triglycerides (MCTs) play essential roles in lipid metabolism and the inhibition of amyloid‐β (Aβ) accumulation. We aimed to explore the possible association between cerebral Aβ deposition and the development of NAFLD and to investigate the effect of DHA combined with MCTs on delaying NAFLD progression and Aβ accumulation. To this end, 40 three‐month‐old APP/PS1 male mice were randomly assigned to 4 groups. The mice were fed a control diet, a DHA (2.91 g/kg) diet, an MCTs (100 g/kg) diet, or a DHA + MCTs diet for 8 months. Ten C57BL/6J mice were fed a control diet and used as the wild‐type (WT) group. The results indicated that APP/PS1 mice exhibited NAFLD and cerebral Aβ accumulation. DHA combined with MCTs decreased blood and liver lipids, relieved hepatic steatosis and fat accumulation, and decreased the level of Aβ in the brain and serum. Moreover, DHA combined with MCTs significantly upregulated the levels of Aβ clearance‐related proteins in the liver, modulated the expression of key hepatic lipid metabolism enzymes and upstream hepatic lipid metabolism factors. In conclusion, compared with wild‐type mice, APP/PS1 mice may be more sensitive to changes in lipid metabolism due to the accumulation of Aβ. DHA combined with MCTs alleviated NAFLD and decreased brain and serum Aβ levels in APP/PS1 mice compared with the control group. The possible mechanism may involve affecting hepatic fat and cholesterol metabolism and increasing hepatic Aβ clearance by modulating liver lipid metabolism enzymes.