Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease

Highlights

• Primary human adipocytes strongly express IRF1 compared with ASC adipocytes

• ASC adipocytes expressing IRF1 exhibit phenotypes associated with metabolic disease

• Adipocyte IRF1 level in vivo leads to recruitment of pro-inflammatory macrophages

• Comparison of in vivo and in vitro adipose inflammation and metabolic phenotypes

Summary

The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes. This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar to its function in other tissues. Utilizing adipose-derived mesenchymal progenitors we subsequently demonstrated that expression of IRF1 in adipocytes indeed contributes to upregulation of inflammatory processes, both in vitro and in vivo. This highlights IRF1's relevance to obesity-related inflammation and the resultant metabolic dysregulation.