CFTR regulates lipid metabolism by relieving adipose inflammation in obesity.

PURPOSE: The downregulation of the cystic fibrosis transmembrane conductance regulator (CFTR) reduces lipogenesis and alters lipid metabolism. However, the role of CFTR in inflammation regulation in adipose tissue has been unknown. This study aims to explore the role of CFTR in adipose inflammation and lipid metabolism and the underlying mechanism using both in vivo and in vitro models. METHODS: We observed the changes in CFTR levels in human adipose tissue, a diet-induced obesity (DIO) mouse model, and 3T3-L1 cells and explored the relationship between CFTR and adipose inflammation. RESULTS: The mRNA expression of CFTR in human omental adipose tissue firstly rose with the BMI and WHR increasing, reached the peak at a BMI of 25-27 kg/m2 and a WHR of 0.8-0.9, and then declined, closely correlated with the serum hs-CRP level. A high-fat diet (HFD) inhibited CFTR expression in adipose tissue and caused the phenotypic transition of M1 to M2-type macrophages. Down-regulation of CFTR led to palmitate-induced adipose inflammation by increasing nuclear factor κB (NF-κB) phosphorylation through GTP-RhoA activation, IKKβ phosphorylation, and the Toll-like receptor 4 (TLR-4)/MyD88/IRAK4 pathway. CONCLUSIONS: CFTR plays a critical role in adipose inflammation regulation and it also represents a potential therapeutic target for the regulation of adipose inflammation and obesity.