Visceral adipocyte size links obesity with dysmetabolism more than fibrosis, and both can be estimated by circulating miRNAs

Yair Pincu, Nataly Makarenkov, Alexandra A. Tsitrina, Marina Rosengarten-Levine, Yulia Haim, Uri Yoel, Idit F. Liberty, Oleg Dukhno, Ivan Kukeev, Matthias Blüher, Isana Veksler-Lublinsky, Assaf Rudich

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Objective: In obesity, adipocyte hypertrophy is detrimental to health, but its' interrelation with fibrosis in the visceral adipose tissue (VAT) depot remains unclear. Because VAT is less accessible via biopsy, biomarkers for VAT quality are needed. The authors hypothesized that VAT adipocyte size and fibrosis are interrelated and can be estimated by circulating microRNAs (circ-miRNAs), contributing to subphenotyping obesity. Methods: Adipocyte size and AT fibrosis were estimated in n = 43 participants (BMI ≥ 30 kg/m2). Circ-miRNAs were sequenced (Next Generation Sequencing). Results: Participants with above- versus below-median VAT adipocyte area exhibited metabolic dysfunction but lower total and pericellular fibrosis. VAT adipocyte size remained associated with metabolic dysfunction even when controlling for BMI or VAT fibrosis in the entire cohort, as in matched-pairs subanalyses. Next Generation Sequencing uncovered 22 and 6 circ-miRNAs associated with VAT adipocyte size and fibrosis, respectively, with miRNA-130b-3p common to both analyses. The combination of miRNA-130b-3p + miR-150-5p + high-density lipoprotein cholesterol discriminated among those with large versus small VAT adipocytes (receiver operating characteristic-area under the curve: 0.872 [95% CI: 0.747–0.996]), whereas miRNA-130b-3p + miRNA-15a-5p + high-density lipoprotein cholesterol discriminated among those with low and high fibrosis (receiver operating characteristic-area under the curve: 0.823 [95% CI: 0.676–0.97]). Conclusions: These findings suggest that VAT adipocyte size and fibrosis are inversely correlated in obesity and can be estimated by distinct circ-miRNAs, providing a potential tool to subphenotype obesity via a liquid biopsy-like approach to assess VAT health in nonsurgical patients.

Original languageEnglish
Pages (from-to)2986-2997
Number of pages12
JournalObesity
Volume31
Issue number12
DOIs
StatePublished - 1 Dec 2023

ASJC Scopus subject areas

  • Endocrinology
  • Nutrition and Dietetics
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism

Fingerprint

Dive into the research topics of 'Visceral adipocyte size links obesity with dysmetabolism more than fibrosis, and both can be estimated by circulating miRNAs'. Together they form a unique fingerprint.

Cite this