Macadamia (Macadamia integrifolia) Oil Prevents High-Fat Diet-Induced Lipid Accumulation and Oxidative Stress by Activating the AMPK/Nrf2 Pathway

Hyperlipidemia, characterized by an abnormal lipid metabolism, is related to multiple cardiovascular diseases that pose challenges to global public health. Macadamia oil (MO), rich in monounsaturated fatty acids (around 80%), is regarded as a functional oil used to regulate lipid accumulation. Nonetheless, the lipid-lowering mechanism of MO is still unknown. Therefore, the lipid-lowering effects of MO in high-fat diet (HFD)-induced hyperlipidemic mice were evaluated in this study. The results revealed that MO could effectively reduce body weight and the organ index and improve serum lipid levels by reducing total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels and elevating high-density lipoprotein cholesterol levels. Additionally, MO supplementation could improve abnormal liver function caused by hyperlipemia, characterized by decreased liver enzyme levels, including alanine aminotransferase and aspartate aminotransferase. Meanwhile, MO also exhibited an inhibitory effect on oxidative stress and lipid accumulation caused by an HFD. Moreover, findings from qRT-PCR and Western blotting analyses suggest that MO supplementation markedly prevented hyperlipidemia by inhibiting the expression of AMPK pathway-related genes, SREBP-1c, FAS, ACC, and PPAR-γ, as well as upregulating the levels of Nrf2, HO-1, and γ-GCS. These results indicate that MO attenuates lipid accumulation in vivo via AMPK/Nrf2 pathway activation, suggesting that MO could serve as a dietary supplementation or medication for treating hyperlipidemia.