Open AccessFatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells
Author(s) -
M. Angela,
Yusuke Endo,
Hikari K. Asou,
Takeshi Yamamoto,
Damon J. Tumes,
Hirotake Tokuyama,
Koutaro Yokote,
Toshinori Nakayama
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms13683
Subject(s) - mtorc1 , reprogramming , microbiology and biotechnology , metabolic pathway , peroxisome , beta oxidation , biology , peroxisome proliferator activated receptor , fatty acid , biochemistry , fatty acid metabolism , pi3k/akt/mtor pathway , metabolism , chemistry , signal transduction , cell , gene
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.