Identification of New Genes Involved in Human Adipogenesis and Fat Storage
Open Access
- 27 February 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (2), e31193
- https://doi.org/10.1371/journal.pone.0031193
Abstract
Since the worldwide increase in obesity represents a growing challenge for health care systems, new approaches are needed to effectively treat obesity and its associated diseases. One prerequisite for advances in this field is the identification of genes involved in adipogenesis and/or lipid storage. To provide a systematic analysis of genes that regulate adipose tissue biology and to establish a target-oriented compound screening, we performed a high throughput siRNA screen with primary (pre)adipocytes, using a druggable siRNA library targeting 7,784 human genes. The primary screen showed that 459 genes affected adipogenesis and/or lipid accumulation after knock-down. Out of these hits, 333 could be validated in a secondary screen using independent siRNAs and 110 genes were further regulated on the gene expression level during adipogenesis. Assuming that these genes are involved in neutral lipid storage and/or adipocyte differentiation, we performed InCell-Western analysis for the most striking hits to distinguish between the two phenotypes. Beside well known regulators of adipogenesis and neutral lipid storage (i.e. PPARγ, RXR, Perilipin A) the screening revealed a large number of genes which have not been previously described in the context of fatty tissue biology such as axonemal dyneins. Five out of ten axonemal dyneins were identified in our screen and quantitative RT-PCR-analysis revealed that these genes are expressed in preadipocytes and/or maturing adipocytes. Finally, to show that the genes identified in our screen are per se druggable we performed a proof of principle experiment using an antagonist for HTR2B. The results showed a very similar phenotype compared to knock-down experiments proofing the “druggability”. Thus, we identified new adipogenesis-associated genes and those involved in neutral lipid storage. Moreover, by using a druggable siRNA library the screen data provides a very attractive starting point to identify anti-obesity compounds targeting the adipose tissue.This publication has 36 references indexed in Scilit:
- C5a-regulated CCAAT/Enhancer-binding Proteins β and δ Are Essential in Fcγ Receptor-mediated Inflammatory Cytokine and Chemokine Production in MacrophagesOnline Journal of Public Health Informatics, 2012
- Behavioral and pharmacologic therapies for obesityNature Reviews Endocrinology, 2010
- The Role of Primary Cilia in Mesenchymal Stem Cell Differentiation: A Pivotal Switch in Guiding Lineage CommitmentCellular and Molecular Bioengineering, 2010
- C/EBP transcription factors regulate SREBP1c gene expression during adipogenesisBiochemical Journal, 2009
- Statistical methods for analysis of high-throughput RNA interference screensNature Methods, 2009
- The Primary Cilium as a Complex Signaling CenterCurrent Biology, 2009
- Consequences of Motor Copy Number on the Intracellular Transport of Kinesin-1-Driven Lipid DropletsCell, 2008
- A probability-based approach for the analysis of large-scale RNAi screensNature Methods, 2007
- Gene Expression Omnibus: NCBI gene expression and hybridization array data repositoryNucleic Acids Research, 2002
- mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.Genes & Development, 1994