A high-fat diet (HFD) is widely recognized as a significant modifiable risk for insulin resistance, inflammation, Type 2 diabetes, atherosclerosis and other metabolic diseases. However, the biological mechanism responsible for key metabolic disorders in the PAT of rabbits subject to HFD remains unclear. Here, untargeted metabolomics (LC-MS/MS) combined with liquid chromatography (LC) and high-resolution mass spectrometry (MS) were used to evaluate PAT metabolic changes. Histological observations showed that the adipocytes cells and density of PAT were significantly increased in HFD rabbits. Our study revealed 206 differential metabolites (21 up-regulated and 185 down-regulated); 47 differential metabolites (13 up-regulated and 34 down-regulated), comprising mainly phospholipids, fatty acids, steroid hormones and amino acids, were chosen as potential biomarkers to help explain metabolic disorders caused by HFD. These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a HFD caused significant lipometabolic disorders. These metabolites may inhibit oxygen respiration by increasing the adipocytes cells and density, cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thus increasing the risk of Type 2 diabetes, atherosclerosis, and other metabolic syndromes.

中文翻译：

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非靶向代谢组学分析揭示了高脂饮食兔肾周脂肪组织的脂肪代谢紊乱

高脂肪饮食 (HFD) 被广泛认为是胰岛素抵抗、炎症、2 型糖尿病、动脉粥样硬化和其他代谢疾病的显着可改变风险。然而，导致 HFD 兔 PAT 关键代谢紊乱的生物学机制仍不清楚。在这里，非靶向代谢组学 (LC-MS/MS) 结合液相色谱 (LC) 和高分辨率质谱 (MS) 用于评估 PAT 代谢变化。组织学观察表明，HFD兔的脂肪细胞和PAT密度显着增加。我们的研究揭示了 206 种差异代谢物（21 种上调，185 种下调）；47 种差异代谢物（13 种上调和 34 种下调），主要包括磷脂、脂肪酸、类固醇激素和氨基酸，被选为潜在的生物标志物，以帮助解释由 HFD 引起的代谢紊乱。这些代谢产物主要与不饱和脂肪酸的生物合成、花生四烯酸代谢途径、卵巢类固醇生成途径和血小板活化途径有关。我们的研究表明，HFD 会导致严重的脂肪代谢紊乱。这些代谢物可能通过增加脂肪细胞和密度来抑制氧呼吸，引起线粒体和内质网功能障碍，产生炎症，最终导致胰岛素抵抗，从而增加患 2 型糖尿病、动脉粥样硬化等代谢综合征的风险。花生四烯酸代谢途径、卵巢类固醇生成途径和血小板活化途径。我们的研究表明，HFD 会导致严重的脂肪代谢紊乱。这些代谢物可能通过增加脂肪细胞和密度来抑制氧呼吸，引起线粒体和内质网功能障碍，产生炎症，最终导致胰岛素抵抗，从而增加患 2 型糖尿病、动脉粥样硬化等代谢综合征的风险。花生四烯酸代谢途径、卵巢类固醇生成途径和血小板活化途径。我们的研究表明，HFD 会导致严重的脂肪代谢紊乱。这些代谢物可能通过增加脂肪细胞和密度来抑制氧呼吸，引起线粒体和内质网功能障碍，产生炎症，最终导致胰岛素抵抗，从而增加患 2 型糖尿病、动脉粥样硬化等代谢综合征的风险。