短期生酮饮食诱导与人类代谢适应相关的全身性脂质组重塑
Short-term ketogenic diet induces systemic lipidomic remodeling associated with metabolic adaptation in humans.
摘要(中文译文)
生酮饮食（ketogenic diet，KD）可诱导全身能量代谢向脂肪酸氧化和酮体生成方向转变，但其对人类脂质分子种水平重塑及胰岛素敏感性的影响仍未完全明确。本研究旨在表征短期生酮饮食对健康成年人循环代谢物和脂质谱的影响及其与胰岛素敏感性的关系。15名参与者（24-38岁）在受控条件下接受为期3天的等热量生酮饮食（75%脂肪、20%蛋白质、5%碳水化合物）。采用代谢组学和脂质组学对干预前后的血清样本进行分析。生酮饮食与循环酰基肉碱、乙酰-L-肉碱和β-羟丁酸升高以及乳酸降低相关，符合脂肪酸氧化和生酮作用增强的表现。脂质组学显示多个脂质类别发生广泛变化，包括总甘油三酯降低以及向更长酰基链和更高不饱和度分子种的转变。醚键磷脂（包括缩醛磷脂）呈升高趋势，而溶血磷脂与磷脂比值降低，提示膜周转发生改变。鞘脂代谢似乎也受到调节，鞘磷脂和己糖神经酰胺水平升高。值得注意的是，特定脂质分子种，包括磷脂酰乙醇胺（16:0/20:5），与胰岛素敏感性指标（QUICKI、HOMA-IR、空腹胰岛素）的变化相关。尽管这些关联需要在更大队列中验证，但其提示脂质分子种水平重塑可能与生酮饮食的短期代谢适应相关。这些发现突显了脂质分子种水平重塑作为人类生酮饮食反应的关键特征，并为未来的机制研究和验证研究提供了基础。
Abstract
The ketogenic diet (KD) induces a shift in systemic energy metabolism toward fatty acid oxidation and ketone body production, but its impact on lipid species-level remodeling and insulin sensitivity in humans remains incompletely characterized. We aimed to characterize short-term KD-induced changes in circulating metabolites and lipid profiles and their relationships with insulin sensitivity in healthy adults. Fifteen participants (24-38 years) underwent a 3-day isocaloric KD (75% fat, 20% protein, 5% carbohydrate) under controlled conditions. Serum samples collected before and after the intervention were profiled using metabolomics and lipidomics. KD was associated with increased circulating acylcarnitines, acetyl-L-carnitine, and -hydroxybutyrate, along with reduced lactate, consistent with enhanced fatty acid oxidation and ketogenesis. Lipidomics showed widespread changes across multiple classes, including lower total triglycerides and shifts toward species with longer acyl chains and higher unsaturation. Ether-linked phospholipids, including plasmalogens, tended to increase, whereas lysophospholipid-to-phospholipid ratios decreased, suggesting altered membrane turnover. Sphingolipid metabolism also appeared to be modulated, with higher sphingomyelin and hexosylceramide levels. Notably, specific lipid species, including phosphatidylethanolamine (16:0/20:5), were correlated with changes in insulin sensitivity indices (QUICKI, HOMA-IR, fasting insulin). Although these associations require validation in larger cohorts, they suggest that lipid species-level remodeling may be linked to short-term metabolic adaptation to KD. These findings highlight lipid species-level remodeling as a key feature of human KD responses and provide a basis for future mechanistic and validation studies.
如何引用
AMA
Minkuk Park, Jae Sik Yu, Justin Y Jeon, Hyun-A Oh, Yong-Ho Lee, Sang-Guk Lee, et al. Short-term ketogenic diet induces systemic lipidomic remodeling associated with metabolic adaptation in humans.. Frontiers in nutrition. 2026; doi:10.3389/fnut.2026.1884256.
APA
Minkuk Park, Jae Sik Yu, Justin Y Jeon, Hyun-A Oh, Yong-Ho Lee, Sang-Guk Lee, et al (2026). Short-term ketogenic diet induces systemic lipidomic remodeling associated with metabolic adaptation in humans.. Frontiers in nutrition. https://doi.org/10.3389/fnut.2026.1884256
GB/T 7714
Minkuk Park, Jae Sik Yu, Justin Y Jeon, Hyun-A Oh, Yong-Ho Lee, Sang-Guk Lee, et al. Short-term ketogenic diet induces systemic lipidomic remodeling associated with metabolic adaptation in humans.[J]. Frontiers in nutrition, 2026 doi:10.3389/fnut.2026.1884256.
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