Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation

Cell Metab. 2018 Sep 4;28(3):504-515.e7. doi: 10.1016/j.cmet.2018.06.002. Epub 2018 Jun 28.


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.

Keywords: AMPK; CD8 T cells; CPT; acetyl-CoA carboxylase; carnitine palmitoyltransferase; etomoxir; fatty acid oxidation; memory T cells; regulatory T cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / physiology*
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / physiology*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Epoxy Compounds / pharmacology*
  • Fatty Acids / metabolism*
  • Female
  • Gene Knockout Techniques
  • Humans
  • Immunologic Memory / drug effects*
  • Lymphocyte Activation / drug effects
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Oxidation-Reduction / drug effects
  • Oxidative Phosphorylation / drug effects
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / metabolism


  • Epoxy Compounds
  • Fatty Acids
  • CPT1B protein, mouse
  • Carnitine O-Palmitoyltransferase
  • Acacb protein, mouse
  • Acetyl-CoA Carboxylase
  • etomoxir