Regulation of human adipogenesis by miR125b-5p

Abstract

MicroRNAs (miRNAs) are non-coding RNAs that regulate target gene expression at the post-transcriptional level and are supposed to be implicated in the control of adipogenesis. We aimed to identify miRNAs which are involved in the regulation of human adipogenesis and searched for their molecular targets.Applying microarray-analysis we identified miR125b-5p as upregulated during human adipocyte differentiation, although its role during adipogenesis is unknown. We identified and characterized the matrix metalloproteinase 11 (MMP11) as a direct target of miR125b-5p by showing that miR125b-5p overexpression significantly reduces MMP11 luciferase activity and mutation of any single binding site was sufficient to abolish the miR125b-5p mediated inhibition of luciferase activity. MMP11 overexpression decreased fat accumulation, indicating that MMP11 acts as an anti-adipogenic regulator. In contrast, overexpression of miR125b-5p itself reduced adipogenesis.In summary, we identified miR125b-5p as upregulated during human adipogenesis indicating that miR125b-5p may serve as a regulator of human adipocyte differentiation. We further show that miR125b-5p downregulates the anti-adipogenic MMP11, but directly inhibits adipogenesis itself. Taken together, these data implicate that miR125b-5p can affect human adipogenesis via MMP11 and probably additional targets.

Multi-Omics Analysis Reveals MicroRNAs Associated With Cardiometabolic Traits

“…Our findings are partly in line with previous research investigating the role of miR-125b-5p on adipogenesis where it is observed that miR-125b-5p downregulates the anti-adipogenic gene MMP11 in human, indicating that miR-125b-5p via MMP11 positively regulate adipogenesis (Rockstroh et al, 2016). Conversely, the same study demonstrated a direct effect of reduction in fat accumulation through overexpression of miR-125b-5p (Rockstroh et al, 2016). In addition to the role of miR-125b-5p on lipid metabolism in human, its regulatory role has been investigated in other organisms including zebrafish and mice.…”

“…Our DNA methylation analysis results showed the association between cg03891346 and waist circumference in the RS. Our findings are partly in line with previous research investigating the role of miR-125b-5p on adipogenesis where it is observed that miR-125b-5p downregulates the anti-adipogenic gene MMP11 in human, indicating that miR-125b-5p via MMP11 positively regulate adipogenesis (Rockstroh et al, 2016). Conversely, the same study demonstrated a direct effect of reduction in fat accumulation through overexpression of miR-125b-5p (Rockstroh et al, 2016).…”

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

“…Several miRNA species, like miR-130 or miR-27b, regulate adipogenic differentiation by targeting the expression of peroxisome proliferator-activated receptor gamma (PPARγ), the master regulator of adipogenesis [47]. Along the same line, miR-125b-5p, which is upregulated during human adipogenesis, downregulates the antiadipogenic matrix metalloproteinase 11 and directly inhibits adipogenesis itself [79]. Zhang et al [76] demonstrated that overexpression of miR-378 apparently prevents and treats obesity by activating the muscle pyruvate-phosphoenolpyruvate futile cycle and enhancing lipolysis in adipose tissue.…”

Altered Regulation of adipomiR Editing with Aging

“…These miRNAs were downregulated in adipose tissue. There are also miRNAs that inhibit adipogenesis but upregulate adipocyte differentiation, such as miR-125 [42] and miR-34a, which target CD36, LXRα, PGC1α, or FASN [42,43]. In addition to adipomiRs, circulating miRNAs such as miR-142, miR-140, miR-138, miR-15a, b and miR-376a are also suggested to be predictive markers for adipose dysfunction [44,45].…”