Department of Biochemistry, University of Wisconsin-Madison, Wisconsin, USA.
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Wisconsin, USA.
J Lipid Res. 2022 Jul;63(7):100197. doi: 10.1016/j.jlr.2022.100197. Epub 2022 Mar 15.
Plasma lipid levels are altered in chronic conditions such as type 2 diabetes and cardiovascular disease as well as during acute stresses such as fasting and cold exposure. Advances in MS-based lipidomics have uncovered a complex plasma lipidome of more than 500 lipids that serve functional roles, including as energy substrates and signaling molecules. This plasma lipid pool is maintained through regulation of tissue production, secretion, and uptake. A major challenge in understanding the lipidome complexity is establishing the tissues of origin and uptake for various plasma lipids, which is valuable for determining lipid functions. Using cold exposure as an acute stress, we performed global lipidomics on plasma and in nine tissues that may contribute to the circulating lipid pool. We found that numerous species of plasma acylcarnitines (ACars) and ceramides (Cers) were significantly altered upon cold exposure. Through computational assessment, we identified the liver and brown adipose tissue as major contributors and consumers of circulating ACars, in agreement with our previous work. We further identified the kidney and intestine as novel contributors to the circulating ACar pool and validated these findings with gene expression analysis. Regression analysis also identified that the brown adipose tissue and kidney are interactors with the plasma Cer pool. Taken together, these studies provide an adaptable computational tool to assess tissue contribution to the plasma lipid pool. Our findings have further implications in understanding the function of plasma ACars and Cers, which are elevated in metabolic diseases.
在慢性疾病（如 2 型糖尿病和心血管疾病）以及急性应激（如禁食和寒冷暴露）期间，血浆脂质水平会发生变化。基于 MS 的脂质组学的进步揭示了超过 500 种具有功能作用的脂质的复杂血浆脂质组，包括作为能量底物和信号分子。通过组织的产生、分泌和摄取的调节，维持了这个血浆脂质池。理解脂质组复杂性的一个主要挑战是确定各种血浆脂质的起源组织和摄取，这对于确定脂质功能很有价值。我们利用寒冷暴露作为急性应激，对可能有助于循环脂质池的血浆和 9 种组织进行了全局脂质组学分析。我们发现，在寒冷暴露后，许多种血浆酰基肉碱（ACars）和神经酰胺（Cers）的含量发生了显著变化。通过计算评估，我们确定肝脏和棕色脂肪组织是循环 ACars 的主要贡献者和消费者，这与我们之前的工作一致。我们进一步确定了肾脏和肠道是循环 ACar 池的新贡献者，并通过基因表达分析验证了这些发现。回归分析还确定了棕色脂肪组织和肾脏与血浆 Cer 池之间存在相互作用。总之，这些研究提供了一种适应性强的计算工具，用于评估组织对血浆脂质池的贡献。我们的研究结果进一步说明了理解代谢疾病中升高的血浆 ACars 和 Cers 的功能的重要性。
