美国麻省理工学院Douglas A. Lauffenburger研究组和波士顿大学医学院Barbara S. Nikolajczyk研究组合作发现，脂肪酸代谢结合减弱β氧化激活人类2型糖尿病中的Th17炎症。 这一研究成果发表在2019年9月3日出版的《细胞—代谢》上。

Th17功能需要脂肪酸摄取，研究人员的最新数据显示阻断CPT1A可抑制2型糖尿病（T2D）患者细胞产生Th17相关细胞因子。来自T2D受试者的免疫细胞中的低CACT：CPT1A比率表明线粒体功能改变并且与这与细胞更偏向通过糖酵解而不是脂肪酸氧化产生ATP的结果一致。然而，糖酵解对Th17细胞因子的产生并不重要。相反，通过对非肥胖受试者的T细胞中的β氧化阻断或CACT敲低可以模拟T2D的特征，并导致细胞利用¹⁶C-脂肪酰基肉碱来促进Th17细胞因子的产生。这些数据显示长链酰基肉碱与受损的β氧化结合可以帮助预测T2D患者的炎症情况。

据悉，调节代谢物和下游能量产生的机制是决定T细胞细胞因子产生的关键因素，但预测肥胖人群代谢状态的Th17谱仍是未知。

附：英文原文

Title: Fatty Acid Metabolites Combine with Reduced β Oxidation to Activate Th17 Inflammation in Human Type 2 Diabetes

Author: Douglas A. Lauffenburger, Barbara S. Nikolajczyk,et al

Issue&Volume: Volume 30 Issue 3

Abstract: Mechanisms that regulate metabolites and downstream energy generation are key determinants of T cell cytokine production, but the processes underlying the Th17 profile that predicts the metabolic status of people with obesity are untested. Th17 function requires fatty acid uptake, and our new data show that blockade of CPT1A inhibits Th17-associated cytokine production by cells from people with type 2 diabetes (T2D). A low CACT:CPT1A ratio in immune cells from T2D subjects indicates altered mitochondrial function and coincides with the preference of these cells to generate ATP through glycolysis rather than fatty acid oxidation. However, glycolysis was not critical for Th17 cytokines. Instead, β oxidation blockade or CACT knockdown in T cells from lean subjects to mimic characteristics of T2D causes cells to utilize 16C-fatty acylcarnitine to support Th17 cytokines. These data show long-chain acylcarnitine combines with compromised β oxidation to promote disease-predictive inflammation in human T2D.

DOI: https://doi.org/10.1016/j.cmet.2019.07.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30377-8#