Chronic Activation of Pattern Recognition Receptors Suppresses Brown Adipogenesis of Multipotent Mesodermal Stem Cells and Brown Preadipocytes

Abstract

Brown adipose tissue (BAT) holds promise to combat obesity through energy‐spending, non‐shivering thermogenesis. Understanding of the regulation of BAT development can lead to novel strategies to increase BAT mass and function for obesity treatment and prevention. Here, we report the effects of chronic activation of pattern recognition receptors on brown adipogenesis of multipotent mesodermal stem C3H10T1/2 cells and immortalized brown preadipocytes derived from classical interscapular BAT of mice. Activation of NOD1, TLR4, or TLR2 by their respective synthetic ligand suppressed brown marker gene expression and lipid accumulation during differentiation of brown‐like adipocytes of C3H10T1/2. Surprisingly, activation of the PRR only during the commitment was sufficient to suppress the differentiation. PRR activation suppressed PGC‐1alpha mRNA, but induced PRDM16 mRNA at the commitment. Consistently, PRR activation suppressed the differentiation of immortalized brown preadipocytes. Activation of PRR induced NF‐κB activation in both cell types, which correlated with their abilities to suppress PPARgamma transactivation, a critical event for brown adipogenesis. Taken together, our results demonstrate that chronic PRR activation suppressed brown adipogenesis of multipotent mesodermal stem cells and brown preadipocytes, possibly through suppression of PPARgamma transactivation. The results suggest that anti‐ inflammatory therapies targeting PRRs may be beneficial for the BAT development.