Endocrine Abstracts

Introduction: Obesity associated with the risks of metabolic syndrome is a rising problem in Western societies but shows a wide depot- and sex-specific variation. A better understanding of the regulatory mechanisms underlying this different depot- and sex-specific role is crucial to identify potential diagnostic and therapeutic targets. MicroRNAs are recently recognized important players in adipogenesis and fat metabolism. They post-transcriptionally regulate diverse biological processes, e.g. the proliferation and differentiation of cells. Here we studied the depot and sex hormone-specific regulation of microRNAs during differentiation. Methods: Inguinal (ING) and epididymal (EPI) white adipose tissue (WAT) of SV40 transfected, stable murine cell lines were used to evaluate fat depot specific expression profiles of selected microRNAs during the development from preadipocytes to mature fat cells both under control conditions and when chronically stimulated with dihydrotestosterone (DHT). Using a microarray approach microRNA candidates which were differentially regulated were identified. Adipocyte differentiation was monitored by Oil-Red-O staining and western blot analysis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were used to validate and characterize candidate microRNAs and their possible targets. These results were confirmed as well in ex vivo separated preadipocytes and mature adipocytes from murine and human WAT depots. Results: In the present study we identified a panel of new microRNAs not related to adipogenesis so far. DHT stimulation decelerates the adipogenesis in both WAT depots, although effects are stronger on EPI WAT differentiation. In line with this, in both WAT depots the expression of most of the analyzed microRNAs decrease in DHT stimulated cells, compared to control treated cell. Conclusion: We identified new microRNAs whose expression is induced during adipogenesis and whose expression extent differs between inguinal and epididymal WAT. These microRNAs, as presumable regulators of adipogenesis, may serve as promising targets for a fat depot directed treatment of obesity.