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Metabolites
Volume 15
Issue 11
10.3390/metabo15110746
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Serum Extracellular Vesicles as Pathogenetic Signals in Obese and Lean Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

by
Chi-Yi Chen
1,†,
Che-Yu Hsu
2,†,
Wei-Pang Chung
3,4,
Hung-Yu Sun
5,
Tzu-Ching Kao
2,
Tzu-Yi Chen
2,
Xing-Min Li
2,
Wei-Lung Huang
2,4,* and
Kung-Chia Young
2,6,*
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia Yi City 600, Taiwan
2
Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan
3
Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan
4
Center of Applied Nanomedicine, National Cheng Kung University, Tainan City 701, Taiwan
5
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan
6
Center of Infectious Disease and Signal Transduction, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Metabolites 2025, 15(11), 746; https://doi.org/10.3390/metabo15110746 (registering DOI)
Submission received: 1 October 2025 / Revised: 5 November 2025 / Accepted: 13 November 2025 / Published: 17 November 2025
(This article belongs to the Section Lipid Metabolism)
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Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and represents a growing healthcare challenge due to its risk of progression and association with metabolic comorbidities. Extracellular vesicles (EVs), nanosized membrane-bound particles mediating intercellular communication, have emerged as candidate biomarkers in multiple diseases. This study aimed to characterize serum EV profiles in MASLD patients, stratified into obese and lean groups using a body mass index cutoff of 23 for Asians. Methods: We enrolled 170 MASLD patients, 83 obese (median age 50, range 20–80) and 87 lean (median age 50, range 20–87), along with 57 non-MASLD controls (median age 44, range 21–86). Serum EV concentrations and particle sizes were quantified using nanoparticle tracking analysis and correlated with clinical and laboratory parameters. EV cargo proteins, including tetraspanins (CD9, CD63) and lipid droplet-associated perilipins (PLIN2, PLIN3), were assessed by Western blotting. Results: Obese MASLD patients displayed marked biochemical abnormalities, whereas lean MASLD patients showed levels comparable to non-MASLD controls. Nevertheless, serum EV concentrations were elevated in both the obese and lean MASLD groups. Importantly, in lean MASLD, EV levels correlated strongly with disruptions in lipid and glycemic homeostasis. Furthermore, a reduction in the PLIN3/CD63 ratio was observed in EVs isolated from lean MASLD patients. Conclusions: Circulating EVs are elevated in both obese and lean MASLD, but lean patients demonstrate a distinctive decrease in the EV PLIN3/CD63 ratio. These findings highlight the potential of EV profiling to uncover disease heterogeneity and to inform risk stratification in MASLD.
Keywords: CD63; extracellular vesicles; lean MASLD; metabolic dysfunction-associated steatotic liver disease; nanoparticle tracking analysis; obese MASLD; perilipins CD63; extracellular vesicles; lean MASLD; metabolic dysfunction-associated steatotic liver disease; nanoparticle tracking analysis; obese MASLD; perilipins
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MDPI and ACS Style

Chen, C.-Y.; Hsu, C.-Y.; Chung, W.-P.; Sun, H.-Y.; Kao, T.-C.; Chen, T.-Y.; Li, X.-M.; Huang, W.-L.; Young, K.-C. Serum Extracellular Vesicles as Pathogenetic Signals in Obese and Lean Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites 2025, 15, 746. https://doi.org/10.3390/metabo15110746

AMA Style

Chen C-Y, Hsu C-Y, Chung W-P, Sun H-Y, Kao T-C, Chen T-Y, Li X-M, Huang W-L, Young K-C. Serum Extracellular Vesicles as Pathogenetic Signals in Obese and Lean Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites. 2025; 15(11):746. https://doi.org/10.3390/metabo15110746

Chicago/Turabian Style

Chen, Chi-Yi, Che-Yu Hsu, Wei-Pang Chung, Hung-Yu Sun, Tzu-Ching Kao, Tzu-Yi Chen, Xing-Min Li, Wei-Lung Huang, and Kung-Chia Young. 2025. "Serum Extracellular Vesicles as Pathogenetic Signals in Obese and Lean Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease" Metabolites 15, no. 11: 746. https://doi.org/10.3390/metabo15110746

APA Style

Chen, C.-Y., Hsu, C.-Y., Chung, W.-P., Sun, H.-Y., Kao, T.-C., Chen, T.-Y., Li, X.-M., Huang, W.-L., & Young, K.-C. (2025). Serum Extracellular Vesicles as Pathogenetic Signals in Obese and Lean Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites, 15(11), 746. https://doi.org/10.3390/metabo15110746

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