Myosteatosis in NAFLD patients correlates with plasma Cathepsin D.

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

doi:10.1515/bmc-2021-0004

Lingling Ding, Jef Verbeek + Show 6 more

Open Access

https://doi.org/10.1515/bmc-2021-0004

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Journal: Biomolecular concepts	Publication Date: Jan 1, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: KU Leuven, Maastricht University

Abstract

Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liver disease (NAFLD). Although it is clear that the liver is a major source of plasma CTSD, it is unknown whether other metabolically active organs such as the muscle, also associate with plasma CTSD levels in NAFLD patients. Therefore, the aim of this study was to explore the relation between lipid accumulation in the muscle (myosteatosis) and plasma CTSD levels in forty-five NAFLD patients. We observed that hepatic steatosis positively associated with plasma CTSD levels, confirming the previously established link between plasma CTSD and the liver. Furthermore, a positive association between myosteatosis and plasma CTSD levels was observed, which was independent of sex, age, BMI, waist circumference and hepatic steatosis. By establishing a positive association between myosteatosis and plasma CTSD levels, our findings suggest that, in addition to the liver, the muscle is also linked to plasma CTSD levels in NAFLD patients. The observed link between myosteatosis and plasma CTSD levels supports the concept of a significant role of the skeletal muscle in metabolic disturbances in metabolic syndrome-related disorders.

Highlights

Due to the growing prevalence of metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD) is an increasing worldwide health problem
Our studies have demonstrated that plasma cathepsin D (CTSD) levels are associated with the development of hepatic inflammation and dyslipidemia, suggesting that plasma CTSD is a key player in metabolic disturbances in NAFLD [4, 6]
We have previously shown that NAFLD progression is positively associated with plasma CTSD levels [6], indicating that increased metabolic dysfunction and inflammation are accompanied by increased plasma CTSD levels

Summary

Introduction

Due to the growing prevalence of metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD) is an increasing worldwide health problem. Studies have shown increased plasma CTSD levels in type 2 diabetes [7], Alzheimer’s disease [8] and inflammatory bowel disease [9], suggesting that extra-hepatic organs are linked to plasma CTSD under pro-inflammatory conditions. Extrahepatic organs such as the gut, adipose tissue and muscle induce metabolic disturbances in MetS and NAFLD, This work is licensed under the Creative Commons

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