Platelet-derived apoptotic vesicles ameliorate nonalcoholic fatty liver disease by regulating lipid metabolism via apolipoprotein A-II

Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a broad range of conditions, commencing with simple steatosis and progressing to nonalcoholic steatohepatitis, with the possibility of further deterioration into fibrosis, cirrhosis, and ultimately, hepatocellular carcinoma. Unfortunately, there is currently no approved medication for treating NAFLD-associated liver steatosis. This underscores the need for improved therapeutic approaches that can modulate lipid metabolism and halt the transition from liver steatosis to chronic liver disease. Our previous studies have demonstrated that apoptotic vesicles (apoVs), which are produced during apoptosis, show great potential in regulating liver homeostasis. However, whether they can ameliorate NAFLD is unknown. In our research, apoVs derived from platelets (PLT-apoVs) as well as apoVs derived from mesenchymal stem cells (MSC-apoVs) were used to treat NAFLD. The results showed that PLT-apoVs exhibited superior effects in diminishing lipid accumulation in liver induced by high-fat diet than MSCapoVs. Through proteomic analysis, we defined and validated apolipoprotein A-II (APOA2) as a regulator for apoV-mediated MSC adipogenesis, which could be used as a target to enhance apoV therapeutic potential in the lipid metabolism biomedical field. Owing to the higher expression of APOA2, PLTapoVs showed better therapeutic effects than MSC-apoVs. Our results pave the way to apoV-based therapy for NAFLD.

Keywords

apolipoprotein A-II / apoptotic vesicles / nonalcoholic fatty liver disease / platelets

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2025 The Author(s). Interdisciplinary Medicine published by Wiley-VCH GmbH on behalf of Nanfang Hospital, Southern Medical University.