microRNAs in der Fettzellen - GEN-AU Cross-species identification of adipo-specific microRNAs in vitro and in vivo

The dramatic increase of overweight and obesity has reached globally the status of the epidemic of the 21st century. Globally, more than 1 billion adults are overweight (BMI > 25) - at least 300 million of them clinically obese (BMI > 30) - and the increasing incidence of obesity in developing countries as well as of child obesity is alarming causing tremendous costs for our health care systems. Obesity is characterized on the cellular level by excess adipose (fat) tissue. The identification of protein-coding genes that are involved in the regulation of fat cell (adipocyte) development has greatly increased our knowledge of the mechanisms that underlie this condition. But still, we are far from a complete picture of molecular events in adipocyte differentiation. Especially, the early stage of adipocyte differentiation is not well understood also due to a lack of appropriate in vitro cell models. Recently, a novel class of tiny regulators - called microRNAs - has been identified to be involved in cellular differentiation which are recruited from the 97% of the human genome that does not encode proteins. To date, more than 350 mouse and 450 human candidates of this novel class of regulators have been identified predicted to regulate 30% of all genes. A small number of microRNAs has been associated with diseases, with the potential for many more. This proposed project addresses the identification of microRNAs regulated across species in the early stage of adipocyte differentiation (adipogenesis) in mammals with relevance in vivo. Therefore, the specific aims of this project are to profile mouse microRNA and mRNA expression during adipogenesis in vitro, to profile mouse microRNA and mRNA expression during adipogenesis in vivo, to identify cross-species regulated microRNAs between human (previous work) and mouse in vitro and in vivo, and to validate adipo-specific miRNAs by inversely regulated target genes. The results obtained will make an important contribution to the understanding molecular mechanisms of fat cell development and the pathogenesis of obesity as one of the most daunting health challenges facing medicine today, thereby also laying the foundations for possible commercial applications.