Insulin resistance is positively associated with plasma cathepsin D activity in NAFLD patients

Lingling Ding, Toon J I De Munck, Yvonne Oligschlaeger, Jef Verbeek, Ger H Koek, Tom Houben, Ronit Shiri-Sverdlov*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Previous studies associated plasma cathepsin D (CTSD) activity with hepatic insulin resistance in overweight and obese humans. Insulin resistance is a major feature of non-alcoholic fatty liver disease (NAFLD) and is one of the multiple hits determining the progression towards non-alcoholic steatohepatitis (NASH). In line, we have previously demonstrated that plasma CTSD levels are increased in NASH patients. However, it is not known whether insulin resistance associates with plasma CTSD activity in NAFLD. To increase our understanding regarding the mechanisms by which insulin resistance mediates NAFLD, fifty-five liver biopsy or MRI-proven NAFLD patients (BMI>25kg/m2) were included to investigate the link between plasma CTSD activity to insulin resistance in NAFLD. We concluded that HOMA-IR and plasma insulin levels are independently associated with plasma CTSD activity in NAFLD patients (standardized coefficient β: 0.412, 95% Cl: 0.142~0.679, p=0.004 and standardized coefficient β: 0.495, 95% Cl: 0.236~0.758, p=0.000, respectively). Together with previous studies, these data suggest that insulin resistance may link to NAFLD via elevation of CTSD activity in plasma. As such, these data pave the way for testing CTSD inhibitors as a pharmacological treatment of NAFLD.

Original languageEnglish
Pages (from-to)110-115
Number of pages6
JournalBiomolecular Concepts
Volume12
Issue number1
DOIs
Publication statusPublished - 9 Aug 2021

Keywords

  • Cathepsin D
  • Humans
  • Insulin Resistance
  • Liver
  • Non-alcoholic Fatty Liver Disease
  • Obesity

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