作者
Dequina A Nicholas, Elizabeth A Proctor, Madhur Agrawal, Anna C Belkina, Stephen C Van Nostrand, Leena Panneerseelan-Bharath, Albert R Jones, Blanche C Ip, Min Zhu, Jose M Cacicedo, Chloe Habib, Nestor Sainz-Rueda, Leah Persky, Patrick G Sullivan, Barbara E Corkey, Caroline M Apovian, Philip A Kern, Douglas A Lauffenburger, Barbara S Nikolajczyk
发表日期
2019/9/3
期刊
Cell metabolism
卷号
30
期号
3
页码范围
447-461. e5
出版商
Elsevier
简介
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 …
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