Related Experiment Video
Updated: May 24, 2026
Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator
Published on: May 19, 2023
Identification of new genes involved in human adipogenesis and fat storage
Jörn Söhle1, Nikolaus Machuy, Elma Smailbegovic
1Beiersdorf AG, Research & Development, Hamburg, Germany.
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.
Insights
Researchers screened 7,784 genes to find new targets for obesity treatment. They identified novel genes involved in fat cell development and lipid storage, including axonemal dyneins, offering new avenues for anti-obesity drug discovery.
Area of Science:
- Molecular Biology
- Genetics
- Metabolic Diseases
Background:
- Obesity is a growing global health challenge requiring novel therapeutic strategies.
- Identifying genes regulating adipogenesis and lipid storage is crucial for developing effective obesity treatments.
Purpose of the Study:
- To systematically analyze genes involved in adipose tissue biology using a high-throughput siRNA screen.
- To identify novel druggable targets for anti-obesity compound screening.
Main Methods:
- Performed a high-throughput siRNA screen of 7,784 human genes in primary adipocytes.
- Validated hits using secondary screens and gene expression analysis.
- Utilized InCell-Western analysis to differentiate between adipogenesis and lipid storage phenotypes.
Main Results:
- Identified 459 genes affecting adipogenesis or lipid accumulation; 333 were validated.
- 110 genes showed altered expression during adipogenesis, including novel regulators like axonemal dyneins.
- Demonstrated druggability of identified targets using an HTR2B antagonist.
Conclusions:
- Discovered new genes associated with adipogenesis and neutral lipid storage.
- The identified genes represent promising targets for developing anti-obesity therapies.
- The screening approach provides a valuable resource for anti-obesity drug discovery.
