Sacha inchi oil alleviates gut microbiota dysbiosis and improves hepatic lipid dysmetabolism in high-fat diet-fed rats

Dietary ω-3 polyunsaturated fatty acids (PUFAs) are beneficial for humans against the development of hyperlipidaemia, but the underlying mechanisms are still poorly understood. Here, we demonstrated that oral consumption of sacha inchi oil, which is rich in α-linolenic acid, alleviated dyslipidemia, hepatic steatosis and inflammatory infiltration in high-fat diet (HFD)-fed rats. Sacha inchi oil administration reversed gut microbiota dysbiosis and altered the gut microbiota metabolome and in particular prevented bile acid dysmetabolism caused by a HFD. Sacha inchi oil intake ameliorated hepatic lipid dysmetabolism in HFD-fed rats, via potentiating the biosynthesis and reuptake of bile acids, reducing the de novo lipogenesis, promoting fatty acid beta-oxidation, and alleviating the dysregulation of glycerolipid, glycerophospholipid, and sphingolipid metabolisms. The results showed that dietary sacha inchi oil can alleviate gut microbiota dysbiosis and reduce lipid dysmetabolism in HFD rats, and provide novel insights into the molecular mechanisms by which plant-derived ω-3 PUFAs prevent the development of hyperlipidaemia.

膳食来源的ω-3多不饱和脂肪酸（ω-3 polyunsaturated fatty acids, PUFAs）对人类抵御高脂血症的发生具有益处，但其潜在的作用机制仍不甚明确。本研究证实，口服摄入富含α-亚麻酸（α-linolenic acid）的印加果油（sacha inchi oil），可缓解高脂饮食（high-fat diet, HFD）喂养大鼠的血脂异常、肝脂肪变性及炎性浸润。印加果油干预可逆转肠道菌群失调（gut microbiota dysbiosis），重塑肠道菌群代谢组（gut microbiota metabolome），尤其可阻断高脂饮食诱导的胆汁酸代谢紊乱（bile acid dysmetabolism）。印加果油摄入可改善高脂饮食喂养大鼠的肝脏脂质代谢紊乱，具体机制包括增强胆汁酸的生物合成与重摄取、减少从头脂肪生成（de novo lipogenesis）、促进脂肪酸β氧化（fatty acid beta-oxidation），并缓解甘油脂（glycerolipid）、甘油磷脂（glycerophospholipid）与鞘磷脂（sphingolipid）代谢的失衡。本研究结果表明，膳食印加果油可减轻高脂饮食大鼠的肠道菌群失调与脂质代谢紊乱，为植物源性ω-3多不饱和脂肪酸抵御高脂血症发生的分子机制提供了全新的研究视角。