Cyclophilin B, a molecule chaperone, promotes adipogenesis in 3T3‑L1 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 3T3-L1 adipocyte differentiation. It showed that the expression level of cypB was increased during 3T3-L1 adipocyte differentiation by reverse transcription-quantitative PcR and western blotting analysis. cypB knockdown using short interfering RNA delayed cell cycle progression from the G 1 /S to G 2 /M phase through the mammalian target of rapamycin (mTOR) signaling pathway and inhibited the expression levels of adipogenic transcription factors including peroxisome proliferator-activated receptor γ (PPARγ) and ccAAT-enhancer 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 G 1 /S to G 2 /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 well-known negative regulator of adipogenesis. Taken together, the data suggested that cypB might serve important physiological regulatory roles in 3T3-L1 adipocyte differentiation.

Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated

“…CypB is known to be related to cellular collagen formation and the growth of various cancer cells [266,267]. However CypB's influence extends significantly into the intricate realm of adipogenesis, where it interacts with regulatory factors [268]. Recent evidence highlights the transcriptional upregulation of CypB as a response to ER stress.…”

“…Expanding its functional spectrum, CypB emerges as an important regulator of adipogenesis [268,270]. Existing research has established a compelling link between ER stress and the dampening of adipogenic factors, ultimately leading to reduced fat accumulation [2].…”

“…However, recent investigations have revealed a paradigm shift, as CypB is now recognized for its role in downregulating CHOP expression [271]. Interestingly, the absence of CypB is associated with reduced lipid droplet formation in knockout cells, underscoring an enhanced adipogenic process under conditions of ER stress [268]. Most intriguingly, the alleviation of C/EBPβ repression acts as a catalyst, promoting the activation of C/EBPα and PPARγ, key transcription factors that exert maximal influence during the intermediate to late stages of cellular differentiation [36].…”

“…In summary, this comprehensive review holistically synthesizes the evolving understanding of the multifaceted roles of CypB in the intricate landscape of obesity-induced ER stress [268]. From its active participation in ER stress responses to its pivotal role in the regulation of adipogenesis, CypB's significance reverberates across multiple physiological contexts.…”

Cyclophilin D knockout significantly prevents HCC development in a streptozotocin-induced mouse model of diabetes-linked NASH

“…Cyclophilin A (PPIA, CypA) is a cytosolic enzyme which can be secreted and has been shown to play important roles in inflammation [26,27] and the lifecycle of multiple viruses such as HIV, HCV, and HBV [27][28][29][30]. Cyclophilin B (PPIB, CypB) localizes to the endoplasmic reticulum where it serves as a chaperone, aiding in the folding of nascent proteins such as collagen [31][32][33][34]. Cyclophilin D (PPIF, CypD) is a component of the mitochondrial permeability transition pore (mPTP) where it can influence pore sensitivity and mitochondrial permeability [35][36][37].…”