Circulating miRNAs Detect High vs Low Visceral Adipose Tissue Inflammation in Patients Living With Obesity.

Autor:	Makarenkov N; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel.; Department of Software & Information Systems Engineering, Faculty of Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel., Haim Y; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel., Yoel U; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel.; Endocrinology Unit, Soroka University Medical Center, Beer-Sheva 84101, Israel., Pincu Y; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel., Tarnovscki T; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel., Liberty IF; Diabetes Clinic, Soroka University Medical Center, Beer-Sheva 84101, Israel., Kukeev I; Department of General Surgery B, Soroka University Medical Center, Beer-Sheva 84101, Israel., Baraf L; Endocrinology Unit, Soroka University Medical Center, Beer-Sheva 84101, Israel., Dukhno O; Department of General Surgery B, Soroka University Medical Center, Beer-Sheva 84101, Israel., Zilber O; Goldman Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel., Blüher M; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany., Rudich A; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel., Veksler-Lublinsky I; Department of Software & Information Systems Engineering, Faculty of Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Feb 20; Vol. 109 (3), pp. 858-867.
DOI:	10.1210/clinem/dgad550
Abstrakt:	Context: The severity of visceral adipose tissue (VAT) inflammation in individuals with obesity is thought to signify obesity subphenotype(s) associated with higher cardiometabolic risk. Yet, this tissue is not accessible for direct sampling in the nonsurgical patient. Objective: We hypothesized that circulating miRNAs (circ-miRs) could serve as biomarkers to distinguish human obesity subgroups with high or low extent of VAT inflammation. Methods: Discovery and validation cohorts of patients living with obesity undergoing bariatric surgery (n = 35 and 51, respectively) were included. VAT inflammation was classified into low/high based on an expression score derived from the messenger RNA levels of TNFA, IL6, and CCL2 (determined by reverse transcription polymerase chain reaction). Differentially expressed circ-miRs were identified, and their discriminative power to detect low/high VAT inflammation was assessed by receiver operating characteristic-area under the curve (ROC-AUC) analysis. Results: Fifty three out of 263 circ-miRs (20%) were associated with high-VAT inflammation according to Mann-Whitney analysis in the discovery cohort. Of those, 12 (12/53 = 23%) were differentially expressed according to Deseq2, and 6 significantly discriminated between high- and low-VAT inflammation with ROC-AUC greater than 0.8. Of the resulting 5 circ-miRs that were differentially abundant in all 3 statistical approaches, 3 were unaffected by hemolysis and validated in an independent cohort. Circ-miRs 181b-5p, 1306-3p, and 3138 combined with homeostatic model assessment of insulin resistance (HOMA-IR) exhibited ROC-AUC of 0.951 (95% CI, 0.865-1) and 0.808 (95% CI, 0.654-0.963) in the discovery and validation cohorts, respectively, providing strong discriminative power between participants with low- vs high-VAT inflammation. Predicted target genes of these miRNAs are enriched in pathways of insulin and inflammatory signaling, circadian entrainment, and cellular senescence. Conclusion: Circ-miRs that identify patients with low- vs high-VAT inflammation constitute a putative tool to improve personalized care of patients with obesity. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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