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@ARTICLE{Chasseigneaux:289316,
      author       = {S. Chasseigneaux and V. Cochois-Guégan and L. Lecorgne and
                      M. Lochus and S. Nicolic and C. Blugeon and L. Jourdren and
                      D. Gomez-Zepeda$^*$ and S. Tenzer$^*$ and S. Sanquer and V.
                      Nivet-Antoine and M.-C. Menet and J.-L. Laplanche and X.
                      Declèves and S. Cisternino and B. Saubaméa},
      title        = {{F}asting upregulates the monocarboxylate transporter
                      {MCT}1 at the rat blood-brain barrier through {PPAR} δ
                      activation.},
      journal      = {Fluids and barriers of the CNS},
      volume       = {21},
      number       = {1},
      issn         = {1743-8454},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2024-00711},
      pages        = {33},
      year         = {2024},
      note         = {HI-TRON},
      abstract     = {The blood-brain barrier (BBB) is pivotal for the
                      maintenance of brain homeostasis and it strictly regulates
                      the cerebral transport of a wide range of endogenous
                      compounds and drugs. While fasting is increasingly
                      recognized as a potential therapeutic intervention in
                      neurology and psychiatry, its impact upon the BBB has not
                      been studied. This study was designed to assess the global
                      impact of fasting upon the repertoire of BBB transporters.We
                      used a combination of in vivo and in vitro experiments to
                      assess the response of the brain endothelium in male rats
                      that were fed ad libitum or fasted for one to three days.
                      Brain endothelial cells were acutely purified and
                      transcriptionaly profiled using RNA-Seq. Isolated brain
                      microvessels were used to assess the protein expression of
                      selected BBB transporters through western blot. The
                      molecular mechanisms involved in the adaptation to fasting
                      were investigated in primary cultured rat brain endothelial
                      cells. MCT1 activity was probed by in situ brain
                      perfusion.Fasting did not change the expression of the main
                      drug efflux ATP-binding cassette transporters or
                      P-glycoprotein activity at the BBB but modulated a
                      restrictive set of solute carrier transporters. These
                      included the ketone bodies transporter MCT1, which is
                      pivotal for the brain adaptation to fasting. Our findings in
                      vivo suggested that PPAR δ, a major lipid sensor, was
                      selectively activated in brain endothelial cells in response
                      to fasting. This was confirmed in vitro where
                      pharmacological agonists and free fatty acids selectively
                      activated PPAR δ, resulting in the upregulation of MCT1
                      expression. Moreover, dosing rats with a specific PPAR δ
                      antagonist blocked the upregulation of MCT1 expression and
                      activity induced by fasting.Altogether, our study shows that
                      fasting affects a selected set of BBB transporters which
                      does not include the main drug efflux transporters.
                      Moreover, we describe a previously unknown selective
                      adaptive response of the brain vasculature to fasting which
                      involves PPAR δ and is responsible for the up-regulation of
                      MCT1 expression and activity. Our study opens new
                      perspectives for the metabolic manipulation of the BBB in
                      the healthy or diseased brain.},
      keywords     = {Blood-brain barrier (Other) / Endothelial cells (Other) /
                      Fasting (Other) / MCT1 (Other) / PPAR δ (Other)},
      cin          = {D191},
      ddc          = {610},
      cid          = {I:(DE-He78)D191-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38589879},
      doi          = {10.1186/s12987-024-00526-8},
      url          = {https://inrepo02.dkfz.de/record/289316},
}