Imbalance of mitochondrial fusion in peripheral blood mononuclear cells is associated with liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis
Thanaput Kunlayawutipong,
Nattayaporn Apaijai,
Kanokkan Tepmalai,
Sarawut Kongkarnka,
Apinya Leerapun,
Kanokporn Pinyopornpanish,
Atiwat Soontornpun,
Siriporn C. Chattipakorn,
Nipon Chattipakorn,
Kanokwan Pinyopornpanish
Affiliations
Thanaput Kunlayawutipong
Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Nattayaporn Apaijai
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
Kanokkan Tepmalai
Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Sarawut Kongkarnka
Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Apinya Leerapun
Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Kanokporn Pinyopornpanish
Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Atiwat Soontornpun
Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Siriporn C. Chattipakorn
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
Nipon Chattipakorn
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
Kanokwan Pinyopornpanish
Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Corresponding author. Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Mitochondrial dysfunction and inflammation contribute to the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). This study aims to evaluate the potential association between mitochondrial dynamics and cell death markers from peripheral blood mononuclear cells (PBMCs) and the presence of MASH with significant liver fibrosis among metabolic dysfunction-associated steatotic liver disease (MASLD) patients. Consecutive patients undergoing bariatric surgery from January to December 2022 were included. Patients with histologic steatosis were classified into MASH with significant fibrosis (F2-4) group or MASLD/MASH without significant fibrosis group (F0-1). Mitochondrial dynamic proteins and cell death markers were extracted from PBMCs. A total of 23 MASLD/MASH patients were included (significant fibrosis group, n = 7; without significant fibrosis group, n = 16). Of the mitochondrial dynamics and cell death markers evaluated, OPA1 protein, a marker of mitochondrial fusion is higher in MASH patients with significant fibrosis compared to those without (0.861 ± 0.100 vs. 0.560 ± 0.260 proportional to total protein, p = 0.001). Mitochondrial fusion/fission (OPA1/DRP1) ratio is significantly higher in MASH patients with significant fibrosis (1.072 ± 0.307 vs. 0.634 ± 0.313, p = 0.009). OPA1 (per 0.01 proportional to total protein) was associated with the presence of significant liver fibrosis with an OR of 1.08 (95%CI, 1.01–1.15, p = 0.035), and adjusted OR of 1.10 (95%CI, 1.00–1.21, p = 0.042). OPA1 from PBMCs is associated with MASH and substantial fibrosis. Future studies should explore if OPA1 could serve as a novel non-invasive liver fibrosis marker.
