TY  - JOUR
AU  - Meroni, Marica
AU  - De Caro, Emilia
AU  - Chiappori, Federica
AU  - Longo, Miriam
AU  - Paolini, Erika
AU  - Mosca, Ettore
AU  - Merelli, Ivan
AU  - Lombardi, Rosa
AU  - Badiali, Sara
AU  - Maggioni, Marco
AU  - Orro, Alessandro
AU  - Mezzelani, Alessandra
AU  - Valenti, Luca
AU  - Fracanzani, Anna Ludovica
AU  - Dongiovanni, Paola
TI  - Hepatic and adipose tissue transcriptome analysis highlights a commonly deregulated autophagic pathway in severe MASLD
JO  - Obesity
VL  - 32
IS  - 5
SN  - 1071-7323
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2024-00976
SP  - 923 - 937
PY  - 2024
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:38439203
DO  - DOI:10.1002/oby.23996
UR  - https://pub.dzne.de/record/271104
ER  -