ESPE Abstracts (2015) 84 P-2-329

Meteorin-Like (METRNL) Expression in Human Adipose Tissue is Associated with Adipocyte Hypertrophy and Inflammation and is Down-Regulated During Human Adipogenesis

Dennis Löffler, Denise Rockstroh, Julian Schwartze, Kathrin Landgraf & Antje Körner

University of Leipzig, Center of Pediatric Research, Leipzig, Germany

Background: The new adipokine/myokine meteorin-like (Metrnl) has been proposed to be of interest for obesity and metabolic disease through its potential role for brown/beige fat thermogenesis and macrophage activation in mice. METRNL was reported to be expressed in white adipose tissue (AT) and upregulated during adipogenesis and by exercise and.

Aims: In this study we analysed the expression of METRNL during human adipogenesis and its regulation by metabolic regulators. Furthermore, we compared its expression in AT components from lean and obese children of our Leipzig Childhood Adipose Tissue cohort (n=103), and analysed associations with obesity and metabolic parameters.

Results: Metrnl was down-regulated during human adipogenesis of SGBS preadipocytes on mRNA (to 22.7±13%) and protein level. Dexamethasone inhibited METRNL expression to 65±6% in preadipocytes but not adipocytes, while insulin, IGF1 and isoproterenol had no effect. In human AT samples, METRNL expression was fivefold higher in SVFs compared to adipocytes. In adipocytes, but not in whole AT or SVF, obese children showed higher expression compared to lean children (7.1±4.0 vs 5.0±2.5; P=0.003) and in both, adipocyte and SVF METRNL expression correlated with BMI-SDS (r=0.33, P=0.001 and r=0.24, P=0.002) and adipocyte size (r=0.26, P=0.005 and r=0.28, P=0.03), but not with adipocyte number. METRNL expression in SVF was negatively related to experimental cell doubling time (r=−0.40, P=0.008). AT samples containing brown adipocytes, as indicated by histology and high UCP1 expression, did not show higher METRNL expression compared to UCP1-negative samples. METRNL expression in adipocytes correlated with HOMA-IR as a marker of insulin resistance, macrophage number and CD68 expression, which was, however, not independent from BMI.

Conclusion: In AT of children, METRNL is expressed in adipocytes and SVF in relation with BMI-SDS but shows a fivefold higher expression in SVF. The down-regulation of METRNL during adipocyte differentiation, the negative association in SFV with proliferation potential, and the positive association with adipocyte size may indicate that METRNL is associated with hypertrophic AT and may explain the association with markers of insulin resistance and AT inflammation.

Funding: This work was supported by grants from the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001 (IFB AdiposityDiseases) and the German Research Council (DFG) for the Clinical Research Center ‘Obesity Mechanisms’ CRC1052/1 C05.

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