[PDF][PDF] Etomoxir actions on regulatory and memory T cells are independent of Cpt1a-mediated fatty acid oxidation

B Raud, DG Roy, AS Divakaruni, TN Tarasenko… - Cell metabolism, 2018 - cell.com
B Raud, DG Roy, AS Divakaruni, TN Tarasenko, R Franke, EH Ma, B Samborska, WY Hsieh…
Cell metabolism, 2018cell.com
T cell subsets including effector (T eff), regulatory (T reg), and memory (T mem) cells are
characterized by distinct metabolic profiles that influence their differentiation and function.
Previous research suggests that engagement of long-chain fatty acid oxidation (LC-FAO)
supports Foxp3+ T reg cell and T mem cell survival. However, evidence for this is mostly
based on inhibition of Cpt1a, the rate-limiting enzyme for LC-FAO, with the drug etomoxir.
Using genetic models to target Cpt1a specifically in T cells, we dissected the role of LC-FAO …
Summary
T cell subsets including effector (Teff), regulatory (Treg), and memory (Tmem) cells are characterized by distinct metabolic profiles that influence their differentiation and function. Previous research suggests that engagement of long-chain fatty acid oxidation (LC-FAO) supports Foxp3+ Treg cell and Tmem cell survival. However, evidence for this is mostly based on inhibition of Cpt1a, the rate-limiting enzyme for LC-FAO, with the drug etomoxir. Using genetic models to target Cpt1a specifically in T cells, we dissected the role of LC-FAO in primary, memory, and regulatory T cell responses. Here we show that the ACC2/Cpt1a axis is largely dispensable for Teff, Tmem, or Treg cell formation, and that the effects of etomoxir on T cell differentiation and function are independent of Cpt1a expression. Together our data argue that metabolic pathways other than LC-FAO fuel Tmem or Treg differentiation and suggest alternative mechanisms for the effects of etomoxir that involve mitochondrial respiration.
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