Myosteatosis in NAFLD patients correlates with plasma Cathepsin D

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.

Myosteatosis: Diagnosis, pathophysiology and consequences in metabolic dysfunction-associated steatotic liver disease

“…5 ), but further investigations are required to determine its precise role in the pathogenesis of myosteatosis in MASLD. 140 …”

Impact of Sarcopenia and Myosteatosis in Non-Cirrhotic Stages of Liver Diseases: Similarities and Differences across Aetiologies and Possible Therapeutic Strategies

“…Calcium overload favours the fusion between lysosomes and plasma membrane, with the release of cathepsin D and other enzymes [ 144 ]. Cathepsin D could induce lipid accumulation into cells, with consequent myosteatosis onset [ 145 ]. A recent study conducted by Nachit et al showed an enhanced prevalence of myosteatosis in obese NASH patients and suggested that myosteatosis could reflect the histological features of NASH [ 24 ].…”

All Roads Lead to Cathepsins: The Role of Cathepsins in Non-Alcoholic Steatohepatitis-Induced Hepatocellular Carcinoma

“…In addition to insulin resistance, cathepsins have been linked to the deregulation of the liver metabolism in NAFLD and NASH. Apart from the observation that lipid accumulation in the liver and muscle in NALFD patients is positively associated with the levels of CTSD [ 53 ], multiple studies also point towards the involvement of other cathepsins in the more progressed form of NALFD, NASH. Increased levels of CTSD were observed in NASH patients compared to healthy individuals [ 14 ].…”