College of Food Science, South China Agricultural University, Guangzhou, Guangdong 510642, China.
Institute of Horticulture, Anhui Academy of Agricultural Sciences, Hefei, Anhui 230031, China.
Food Res Int. 2024 Dec;197(Pt 1):115141. doi: 10.1016/j.foodres.2024.115141. Epub 2024 Sep 26.
The mechanisms underlying the ameliorative effects of polyunsaturated fatty acids (PUFAs) on metabolic disorders induced by a high-fat diet (HFD) remain poorly unclear. In this study, we investigated the anti-hyperlipidemic effects of Trichosanthes kirilowii Maxim. (T. kirilowii) seed oil rich in conjugated linolenic acid in HFD-induced hyperlipidemic rats, by the gut microbiome, cecum bile acids (BAs), and serum metabolomics. The results showed that T. kirilowii seed oil improved dyslipidemia, hepatic steatosis, oxidative stress, and inflammatory responses in HFD-induced rats. Meanwhile, T. kirilowii seed oil inhibited sterol regulatory element-binding protein 1c (SREBP-1c) mediated fatty acid synthesis and upregulated cholesterol 7-alpha hydroxylase (CYP7A1) mediated hepatic cholesterol metabolism to exert hypolipidemic effects. The administration of high dose T. kirilowii seed oil (THD) improved gut microbiota dysbiosis, increased the relative abundance of beneficial bacteria Romboutsia and unidentified_Oscillospiraceae, and decreased the relative abundance of Christensenellaceae_R-7 group, Phascolarctobacterium, and Bacteroides in HFD-induced rats. T. kirilowii seed oil reduced the accumulation of cecum primary BAs in HFD-induced rats. In addition, THD reversed the HFD-induced changes in 24 serum metabolites including leucine, isoleucine, acetylcarnitine, and glucose. Metabolic pathway enrichment analysis of the differential metabolites revealed that valine, leucine and isoleucine metabolism, butanoate metabolism, citrate cycle, and glycolysis were potential metabolic pathways involved in the anti-hyperlipidemic effects of T. kirilowii seed oil. In conclusion, this study found that dietary T. kirilowii seed oil alleviated gut microbiota dysbiosis and improved metabolic disorders in hyperlipidemic rats. This provides new insights into the anti-hyperlipidemic mechanism by which other families of PUFAs are derived from different plants.
多不饱和脂肪酸（PUFAs）对高脂肪饮食（HFD）诱导的代谢紊乱的改善作用的机制尚不清楚。在这项研究中，我们通过肠道微生物群、盲肠胆汁酸（BAs）和血清代谢组学研究了富含共轭亚油酸的苦瓜籽油对 HFD 诱导的高脂血症大鼠的抗高脂血症作用。结果表明，苦瓜籽油改善了 HFD 诱导的大鼠血脂异常、肝脂肪变性、氧化应激和炎症反应。同时，苦瓜籽油抑制固醇调节元件结合蛋白 1c（SREBP-1c）介导的脂肪酸合成，并上调胆固醇 7-α羟化酶（CYP7A1）介导的肝胆固醇代谢，发挥降血脂作用。高剂量苦瓜籽油（THD）改善了肠道微生物群失调，增加了有益细菌 Romboutsia 和未鉴定的 Oscillospiraceae 的相对丰度，降低了 Christensenellaceae_R-7 组、Phascolarctobacterium 和 Bacteroides 在 HFD 诱导的大鼠中的相对丰度。苦瓜籽油减少了 HFD 诱导的大鼠盲肠初级 BAs 的积累。此外，THD 逆转了 HFD 诱导的 24 种血清代谢物的变化，包括亮氨酸、异亮氨酸、乙酰肉碱和葡萄糖。差异代谢物的代谢途径富集分析表明，缬氨酸、亮氨酸和异亮氨酸代谢、丁酸盐代谢、柠檬酸循环和糖酵解可能是苦瓜籽油抗高脂血症作用的潜在代谢途径。总之，本研究发现，膳食苦瓜籽油缓解了高脂血症大鼠的肠道微生物群失调和代谢紊乱。这为其他植物来源的 PUFAs 家族提供了新的见解，了解其抗高脂血症的作用机制。
