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@ARTICLE{He:164641,
      author       = {He, Wei and Henne, Antonia and Lauterbach, Mario and
                      Geißmar, Eike and Nikolka, Fabian and Kho, Celia and Heinz,
                      Alexander and Dostert, Catherine and Grusdat, Melanie and
                      Cordes, Thekla and Härm, Janika and Goldmann, Oliver and
                      Ewen, Anouk and Verschueren, Charlène and Blay-Cadanet,
                      Julia and Geffers, Robert and Garritsen, Hendrikus and
                      Kneiling, Manfred and Holm, Christian K and Metallo,
                      Christian M and Medina, Eva and Abdullah, Zeinab and Latz,
                      Eicke and Brenner, Dirk and Hiller, Karsten},
      title        = {{M}esaconate is synthesized from itaconate and exerts
                      immunomodulatory effects in macrophages.},
      journal      = {Nature metabolism},
      volume       = {4},
      number       = {5},
      issn         = {2522-5812},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DZNE-2022-01171},
      pages        = {524 - 533},
      year         = {2022},
      abstract     = {Since its discovery in inflammatory macrophages, itaconate
                      has attracted much attention due to its antimicrobial and
                      immunomodulatory activity1-3. However, instead of
                      investigating itaconate itself, most studies used
                      derivatized forms of itaconate and thus the role of
                      non-derivatized itaconate needs to be scrutinized.
                      Mesaconate, a metabolite structurally very close to
                      itaconate, has never been implicated in mammalian cells.
                      Here we show that mesaconate is synthesized in inflammatory
                      macrophages from itaconate. We find that both,
                      non-derivatized itaconate and mesaconate dampen the
                      glycolytic activity to a similar extent, whereas only
                      itaconate is able to repress tricarboxylic acid cycle
                      activity and cellular respiration. In contrast to itaconate,
                      mesaconate does not inhibit succinate dehydrogenase. Despite
                      their distinct impact on metabolism, both metabolites exert
                      similar immunomodulatory effects in pro-inflammatory
                      macrophages, specifically a reduction of interleukin (IL)-6
                      and IL-12 secretion and an increase of CXCL10 production in
                      a manner that is independent of NRF2 and ATF3. We show that
                      a treatment with neither mesaconate nor itaconate impairs
                      IL-1β secretion and inflammasome activation. In summary,
                      our results identify mesaconate as an immunomodulatory
                      metabolite in macrophages, which interferes to a lesser
                      extent with cellular metabolism than itaconate.},
      keywords     = {Animals / Inflammasomes / Macrophages: drug effects /
                      Macrophages: metabolism / Mice / RAW 264.7 Cells /
                      Succinates: metabolism / Succinates: pharmacology /
                      Inflammasomes (NLM Chemicals) / Succinates (NLM Chemicals) /
                      itaconic acid (NLM Chemicals)},
      cin          = {AG Latz ; AG Latz},
      ddc          = {610},
      cid          = {I:(DE-2719)1013024},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9744384},
      pubmed       = {pmid:35655024},
      doi          = {10.1038/s42255-022-00565-1},
      url          = {https://pub.dzne.de/record/164641},
}