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@ARTICLE{Papa:646269,
      author       = {Papa, Christina and Rose, Alina and Martin, Hugo N. G. and
                      Useini, Abibe and Geier, Florian and Liao, Longsheng and
                      Rodríguez-Aguilera, Jesús Rafael and Valina-Allo, Philipp
                      and Hoffmann, Anne and Tvardovskiy, Andrey and Zulfqar,
                      Faiqa and Zimmerman, Andrea and Schicht, Gerda and Ott,
                      Fritzi and Körner, Christiane and Engelmann, Beatrice and
                      Rolle-Kampczyk, Ulrike and von Bergen, Martin and Meier,
                      Matthias and Bartke, Till and Seehofer, Daniel and Klöting,
                      Nora and Matz-Soja, Madlen and Damm, Georg and Boeckel,
                      Jes-Niels and Buescher, Joerg M. and Blüher, Matthias and
                      Laufs, Ulrich and Bondareva, Olga and Sträter, Norbert and
                      Künze, Georg and Heiker, John T. and Sheikh, Bilal N.},
      title        = {{B}empedoic acid directly binds and activates {PPAR}α},
      journal      = {Cell metabolism},
      volume       = {xx},
      issn         = {1550-4131},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {PUBDB-2026-00792},
      pages        = {S1550413125005492},
      year         = {2026},
      abstract     = {Bempedoic acid (BA) is a recently approved drug that lowers
                      cholesterol and hepatic lipids, yet its mechanism of action
                      remains incompletely understood. Here, we combine
                      transcriptomic, biochemical, and structural approaches to
                      show that BA directly binds to and activates peroxisome
                      proliferator-activated receptor alpha (PPARα). BA treatment
                      robustly induced PPARα signaling and fatty acid oxidation
                      in primary hepatocytes and mouse liver. Through X-ray
                      crystallography, we uncovered that BA binds to the
                      ligand-binding domain of PPARα and stabilizes its active
                      conformation. BA activated PPARα target genes independently
                      of very-long-chain acyl-coenzyme A (CoA) synthetase
                      (ACSVL1), the liver-enriched enzyme that converts BA to its
                      bempedoyl-CoA form. Notably, BA-mediated induction of fatty
                      acid oxidation required PPARα. Together, this work reveals
                      direct PPARα activation as a key mechanism of BA action,
                      providing a molecular basis for its lipid-lowering effects
                      and suggesting broader therapeutic potential beyond the
                      liver.},
      cin          = {EMBL-User},
      ddc          = {570},
      cid          = {I:(DE-H253)EMBL-User-20120814},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P14-20150101},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1016/j.cmet.2025.12.018},
      url          = {https://bib-pubdb1.desy.de/record/646269},
}