Cyclophilin B, a molecule chaperone, promotes adipogenesis in 3T3­L1 preadipocytes via AKT/mTOR pathway.

ABSTRACT

Cyclophilin is known to act as a molecular chaperone in the endoplasmic reticulum. Recent studies have reported that the expression of cyclophilin B (CypB) is increased in ob/ob mice and its inhibitor suppresses adipocyte differentiation. However, the mechanism of action of CypB in adipocytes remains to be elucidated. The present study investigated the role of CypB in 3T3­L1 adipocyte differentiation. It showed that the expression level of CypB was increased during 3T3­L1 adipocyte differentiation by reverse transcription­quantitative PCR and western blotting analysis. CypB knockdown using short interfering RNA delayed cell cycle progression from the G1/S to G2/M phase through the mammalian target of rapamycin (mTOR) signaling pathway and inhibited the expression levels of adipogenic transcription factors including peroxisome proliferator­activated receptor Î³ (PPARγ) and CCAAT­enhancer binding protein (C/EBP)α. Additionally, the accumulation of lipid droplets was inhibited by CypB knockdown. Conversely, overexpression of CypB promoted cell cycle progression from the G1/S to G2/M phase by the mTOR signaling pathway and enhanced the expression levels of adipogenic transcription factors including PPARγ and C/EBPα. Finally, the present study showed that CypB downregulated the expression of CHOP, a well­known negative regulator of adipogenesis. Taken together, the data suggested that CypB might serve important physiological regulatory roles in 3T3­L1 adipocyte differentiation.