The Important Role of Phosphatidylserine, ADAM17, TNF-Alpha, and Soluble MER on Efferocytosis Activity in Central Obesity

• Published in: Journal of obesity Vol. 2024; pp. 1424404 - 10
• Main Authors: Purnama, Chandra Agung, Meiliana, Anna, Barliana, Melisa Intan, Lestari, Keri, Wijaya, Andi
• Format: Journal Article
• Language: English
• Published: United States Hindawi 20-03-2024; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: ADAM17 Protein; Adipocytes; Analysis; Autoimmune diseases; Biomarkers; Body fat; Body mass index; Cell death; Cholesterol; Cross-Sectional Studies; Cytokines; Diabetes; Efferocytosis; Enzyme kinetics; High density lipoprotein; Humans; Inflammation; Kinases; Liver; Male; Metabolic disorders; Metabolic syndrome; Obesity; Obesity, Abdominal; Phagocytosis; Phosphatidylserines; Phospholipids; Proteins; Questionnaires; Tumor necrosis factor; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Type 2 diabetes; Indonesia; United States > US; Asia-Pacific region
• ISSN: 2090-0708; 2090-0716
• DOI: 10.1155/2024/1424404

Background. Obesity is expected to hinder efferocytosis due to ADAM17-mediated cleavage of the MER tyrosine kinase receptor, producing soluble MER (sMER) that disrupts MERTK binding to cell death markers. However, the intracellular efferocytosis pathway in central obesity remains elusive, particularly the role of low-grade chronic inflammation in its initiation and identification of binding signals that disrupt efferocytosis. Objective. We investigate the efferocytosis signaling pathway in men with central obesity and its relationship with inflammation, cell death, and related processes. Methods. A cross-sectional study was conducted, and clinical data and blood samples were collected from 56 men with central obesity (obese group) and 29 nonobese individuals (control group). Clinical evaluations and predefined biochemical screening tests were performed. The efferocytosis signaling pathway was investigated by measuring phosphatidylserine (PS), ADAM17, TNF-alpha (TNF-α), and sMER. Results. Metabolic syndrome was detected in more than half of the participants in the obese group according to the predefined tests. Mean levels of PS, TNF-α, and sMER were higher in the obese group but not significantly different from those of the control group. Further analysis based on waist circumference (WC) ranges in the obese group revealed a significant increase in PS and sMER levels between the control group and the obese group with WC greater than 120 cm. ADAM17 levels were significantly higher in the obese group than in the control group. PS was positively correlated with WC and ADAM17. ADAM17 was positively correlated with TNF-α and sMER, indicating impaired efferocytosis. Conclusions. Central obesity appeared to cause a disturbance in efferocytosis that began with cell damage and death, along with an enlargement of the WC and an ongoing inflammatory response. Efferocytosis was disrupted by proinflammatory cytokine regulators, which induced the production of sMER and interfered with the efferocytosis process.