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@ARTICLE{Meroni:271104,
      author       = {Meroni, Marica and De Caro, Emilia and Chiappori, Federica
                      and Longo, Miriam and Paolini, Erika and Mosca, Ettore and
                      Merelli, Ivan and Lombardi, Rosa and Badiali, Sara and
                      Maggioni, Marco and Orro, Alessandro and Mezzelani,
                      Alessandra and Valenti, Luca and Fracanzani, Anna Ludovica
                      and Dongiovanni, Paola},
      title        = {{H}epatic and adipose tissue transcriptome analysis
                      highlights a commonly deregulated autophagic pathway in
                      severe {MASLD}},
      journal      = {Obesity},
      volume       = {32},
      number       = {5},
      issn         = {1071-7323},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DZNE-2024-00976},
      pages        = {923 - 937},
      year         = {2024},
      abstract     = {The incidence of metabolic dysfunction-associated steatotic
                      liver disease (MASLD) is rapidly ramping up due to the
                      spread of obesity, which is characterized by expanded and
                      dysfunctional visceral adipose tissue (VAT). Previous
                      studies have investigated the hepatic transcriptome across
                      MASLD, whereas few studies have focused on VAT.We performed
                      RNA sequencing in 167 hepatic samples from patients with
                      obesity and in a subset of 79 matched VAT samples.
                      Circulating cathepsin D (CTSD), a lysosomal protease, was
                      measured by ELISA, whereas the autophagy-lysosomal pathway
                      was assessed by Western blot in hepatic and VAT samples (n =
                      20).Inflammation, extracellular matrix remodeling, and
                      mitochondrial dysfunction were upregulated in severe MASLD
                      in both tissues, whereas autophagy and oxidative
                      phosphorylation were reduced. Tissue comparative analysis
                      revealed 13 deregulated genes, including CTSD, which showed
                      the most robust diagnostic accuracy in discriminating mild
                      and severe MASLD. CTSD expression correlated with
                      circulating protein, whose increase was further validated in
                      432 histologically characterized MASLD patients, showing a
                      high accuracy in foreseeing severe liver injury. In
                      addition, the assessment of serum CTSD increased the
                      performance of fibrosis 4 in diagnosing advanced disease.By
                      comparing the hepatic and VAT transcriptome during MASLD, we
                      refined the concept by which CTSD may represent a potential
                      biomarker of severe disease.},
      cin          = {AG Aschenbrenner},
      ddc          = {610},
      cid          = {I:(DE-2719)5000082},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF4-354},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38439203},
      doi          = {10.1002/oby.23996},
      url          = {https://pub.dzne.de/record/271104},
}