Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells

Nat Commun. 2016 Nov 30:7:13683. doi: 10.1038/ncomms13683.

Abstract

To fulfil the bioenergetic requirements for increased cell size and clonal expansion, activated T cells reprogramme their metabolic signatures from energetically quiescent to activated. However, the molecular mechanisms and essential components controlling metabolic reprogramming in T cells are not well understood. Here, we show that the mTORC1-PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4+ T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4+ T cells. PPARγ directly binds and induces genes associated with fatty acid uptake in CD4+ T cells in both mice and humans. The PPARγ-dependent fatty acid uptake programme is critical for metabolic reprogramming. Thus, we provide important mechanistic insights into the metabolic reprogramming mechanisms that govern the expression of key enzymes, fatty acid metabolism and the acquisition of an activated phenotype during CD4+ T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Proliferation / physiology
  • Chromatin Immunoprecipitation
  • Fatty Acids / metabolism*
  • Gene Knockdown Techniques
  • Healthy Volunteers
  • Humans
  • Lymphocyte Activation / physiology*
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • RNA, Small Interfering / metabolism
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases
  • Up-Regulation / physiology

Substances

  • Fatty Acids
  • PPAR gamma
  • RNA, Small Interfering
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases