Lipids & metabolic liver disease

Hepatic and adipose tissue transcriptome analysis highlights a commonly deregulated autophagic pathway in severe MASLD

Obesity (Silver Spring)Published Mechanistic study

Authors' conclusion

By comparing the hepatic and VAT transcriptome during MASLD, we refined the concept by which CTSD may represent a potential biomarker of severe disease.

Study context

Population
Patients with obesity with MASLD; hepatic and visceral adipose tissue (VAT) samples79 matched VAT samples
Participants
167 hepatic samples
Comparison
Severe vs mild MASLD
Outcome
Hepatic and VAT transcriptome pathways in severe vs mild MASLD; CTSD as diagnostic marker of severe MASLD
Methodological detailsRNA sequencing of hepatic and VAT samples; circulating cathepsin D (CTSD) by ELISA; autophagy-lysosomal pathway by Western blot (n = 20)
  • RNA sequencing of hepatic and VAT samples; circulating CTSD by ELISA; autophagy-lysosomal pathway by Western blot (n = 20)

Main finding

As reported in the abstract

Deregulated genes in tissue comparative analysis, including CTSD, which showed the most robust diagnostic accuracy in discriminating mild and severe MASLD

13

CTSD expression correlated with circulating protein; increase validated in histologically characterized MASLD patients, with high accuracy in foreseeing severe liver injury

432 patients

Further findings

Serum CTSD validation in histologically characterized MASLD patients

Circulating CTSD increase validated, with high accuracy in foreseeing severe liver injury; n
432
Serum CTSD increased the performance of fibrosis 4 in diagnosing advanced disease

Original publication

Hepatic and adipose tissue transcriptome analysis highlights a commonly deregulated autophagic pathway in severe MASLD. Obesity (Silver Spring). Published 4 March 2024. doi:10.1002/oby.23996

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