Lantibiotic synthetase C‐like protein 2 (LanCL2) is necessary for 3T3‐L1 Differentiation to Adipocytes

Adipocyte differentiation is a highly regulated process, necessary for metabolic homeostasis and nutrient sensing. The expression of peroxisome proliferator‐activated receptor gamma (PPARγ) and the subsequent transactivation of adipogenic genes is critical for adipogenesis, and is controlled through the coordinated efforts of CCAAT‐enhancer‐binding (C/EBP) proteins and a PPARγ ligand. In this study, we identified lanthionine synthetase C‐like protein 2 (LanCL2), as a positive regulator of adipogenesis in 3T3‐L1 cells. Knockdown of LanCL2, but not LanCL1, inhibited adipocyte differentiation, and this effect was not mediated through cAMP or Akt signaling pathways. The expression of early adipogenic markers C/EBPβ and C/EBPδ remained intact in LanCL2 knockdown cells, and an arrest in differentiation was observed at the stage of PPARγ activation. The addition of a PPARγ ligand, troglitazone rescued differentiation in LanCL2 knockdown cells and restored expression of late adipogenic markers. Furthermore, addition of troglitazone partially restored the transactivation potential of PPARγ. Taken together, our study reveals a novel role of LanCL2 in adipogenesis, acting through the ligand‐mediated activation and/or propagation of PPARγ signaling. Support or Funding Information The work was supported by the Howard Hughes Medical Institute (HHMI)