ABSTRACT
@#【Objective】 To investigate the role of CFTR in visceral preadipocyte proliferation and differentiation.【Method】Primary preadipocytes were separated from visceral adipose tissue of the 4-week-old and 8-week-old CFTR-KO mice and age-matched littermates. Quantitative real time -PCR assay were used to measure the expression of proliferative and differentiation key transcriptional factors in visceral preadipocytes. An in vitro dexamethasone-methylisobutylxanthine- insulin（DMI）induced 3T3-L1 preadipocytes differentiation model was used. Western blot assay was used to measure the change of CFTR and key differentiation transcriptional factors. After knockdown or overexpression of CFTR，western blot， quantitative real time-PCR，MTT assay and Oil red O staining were used to measure the effects of CFTR on 3T3-L1 cells proliferation and differentiation. A mouse model of obesity with high-fat diet was used. Quantitative real time -PCR assay were used to measure the mRNA levels of proliferative and differentiation key transcriptional factors and CFTR in visceral preadipocytes.【Results】CFTR- KO mice displayed a decline in preadipocyte proliferation and differentiation，including Pref-1，CyclinD1，PPAR γ，and C/EBP α（P<0.05）. In vitro，DMI caused significant increases in CFTR expression in the early phase of differentiation （P<0.05）. DMI- stimulated preadipocyte transcriptional factors reflecting proliferative differentiation（C/EBPβ，C/EBP δ，CREB，and KLF4）and adipogenic differentiation（SREBP-1，PPAR γ，and C/EBP α） were markedly inhibited by knockdown，and reversed by overexpression of CFTR. CFTR is expressed in mouse visceral preadipocytes and increased with the enhanced preadipocyte proliferation and differentiation as evidenced by detecting key transcriptional factors including PPAR γ，C/EBP α，C/EBP β，C/EBP δ，SREBP-1 and FABP4 in mice fed with high- fat-diet for 2，4 weeks（P<0.05）.【Conclusions】These results demonstrate that CFTR may play a role in the preadipocyte proliferation and differentiation.