TY - JOUR
T1 - Insulin resistance is positively associated with plasma cathepsin D activity in NAFLD patients
AU - Ding, Lingling
AU - De Munck, Toon J I
AU - Oligschlaeger, Yvonne
AU - Verbeek, Jef
AU - Koek, Ger H
AU - Houben, Tom
AU - Shiri-Sverdlov, Ronit
N1 - Funding Information:
This study gets funding supports from the Dutch Organization for Scientific Research (NWO) (Vidi grant no. 016.126.327), ASPASIA (grant no. 015.008.043), TKI-LSH (grant no. 40-41200-98-9306) and VCK (grant no. Swu16.0057-VT). Lingling Ding is supported by the Chinese Scholarship Council with file number 201709110146.
Publisher Copyright:
© 2021 Lingling Ding et al., published by De Gruyter 2021.
PY - 2021/8/9
Y1 - 2021/8/9
N2 - 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.
AB - 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.
KW - Cathepsin D
KW - Humans
KW - Insulin Resistance
KW - Liver
KW - Non-alcoholic Fatty Liver Disease
KW - Obesity
U2 - 10.1515/bmc-2021-0011
DO - 10.1515/bmc-2021-0011
M3 - Article
C2 - 34370929
SN - 1868-5021
VL - 12
SP - 110
EP - 115
JO - Biomolecular Concepts
JF - Biomolecular Concepts
IS - 1
ER -