Abstract
Obesity, the excess accumulation of adipose tissue, is one of the most pressing health problems in both the Western world and in developing countries. Adipose tissue growth results from two processes: the increase in number of adipocytes (hyperplasia) that develop from precursor cells, and the growth of individual fat cells (hypertrophy) due to incorporation of triglycerides. Adipogenesis, the process of fat cell development, has been extensively studied using various cell and animal models. While these studies pointed out a number of key factors involved in adipogenesis, the list of molecular components is far from complete.The advance of high-throughput technologies has sparked many experimental studies aimed at the identification of novel molecular components regulating adipogenesis. This paper examines the results of recent studies on adipogenesis using high-throughput technologies. Specifically, it provides an overview of studies employing microarrays for gene expression profiling and studies using gel based and non-gel based proteomics as well as a chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) or sequencing (ChIP-seq). Due to the maturity of the technology, the bulk of the available data was generated using microarrays. Therefore these data sets were not only reviewed but also underwent meta analysis.The review also shows that large-scale omics technologies in conjunction with sophisticated bioinformatics analyses can provide not only a list of novel players, but also a global view on biological processes and molecular networks. Finally, developing technologies and computational challenges associated with the data analyses are highlighted, and an outlook on the questions not previously addressed is provided.
Highlights
Since the cloning of the obese gene in 1994 [1] and the subsequent functional characterization of its product, leptin, it has become increasingly evident that adipose tissue is a key organ in the regulation of the body’s energy homeostasis rather than a passive storage of fat
This paper examines the results of recent studies on adipogenesis using high-throughput technologies
The development of white adipose tissue (WAT) is the result of two processes: the increase in number of adipocytes that develop from precursor cells, and the growth of individual fat cells due to incorporation of triglycerides
Summary
Since the cloning of the obese gene in 1994 [1] and the subsequent functional characterization of its product, leptin, it has become increasingly evident that adipose tissue is a key organ in the regulation of the body’s energy homeostasis rather than a passive storage of fat. Another study was employing ChIP followed by pair end-tagging (PET) sequencing technology to identify 7821 Pparg and Rxr binding sites [87] Combining this binding data with gene expression (expression profiles of differentiated and Pparg-silenced 3T3-L1 cells) and validation studies (ChIP-qPCR) yielded 75 high-confidence Pparg:Rxr target genes. In the studies on Scd and Nrip Affymetrix GeneChip analysis was performed on differentiated 3T3-L1 cells transfected with either scrambled or siRNA constructs to elucidate the pathways affected by the silencing of these genes and to place them in the transcriptional cascade Another “top-down” approach for identifying as yet unknown players in adipogenesis was the use of highthroughput DNase I hypersensitivity analysis in conjunction with a computational strategy to identify differentiationdependent cis- and trans-acting factors. A major challenge for these computational approaches is the construction of (weighted-) gene co-expression networks [106] and the inference of gene regulatory networks based on sequence, ChIP-chip, and gene expression data and the ultimate integration of the heterogeneous datasets
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