The Role Of The Chemokine CXCL13 In Adipose Tissue Thermogenesis And Inflammation

Objectives: The occurrence of obesity is closely related to the imbalance of energy metabolism and the excessive accumulation of adipose tissues.Brown adipose tissue(BAT)is mainly responsible for mammalian non-shivering thermogenesis and promotes energy expenditure.Meanwhile,similar like white adipose tissue(WAT),BAT also secretes a variety of adipokines to regulate metabolism through paracrine,autocrine or endocrine ways.The chemokine CXCL13,a B cell chemokine,functions in inflammation and tumor-related diseases.Through gene chip screening,we have previously found that the expression of CXCL13 in adipose tissue was significantly changed under cold stimulation,but the role of CXCL13 in the adipose tissues is unclear.This study aimed to explore the role of adipose chemokine CXCL13 in the regulation of BAT activity and thermogenesis.Methods:(1)The bioinformatic analyses were performed to determine the differential genes in adipose tissues in response to cold stimulation.Flow cytometry was used to analyze the change of immune cell proportion in adipose tissue after cold stimulation.(2)The expression of CXCL13 and its receptor CXCR5 in adipose tissues,including BAT,subcutaneous WAT(SAT)and visceral WAT(VAT),and different tissue components,including mature adipocytes and stromal vascular fraction(SVF),under cold stimulation were detected.(3)The expression of CXCL13 and its receptor CXCR5 in cell and culture medium during the differentiation of mouse primary adipocytes were detected.(4)The brown adipocytes and macrophages were treated with CXCL13,and the expression levels of thermogenesis and inflammation related genes in adipocytes and macrophage marker genes were determined.(5)Recombined CXCL13 was injected into BAT of C57BL/6J male mice,and thermogenesis,inflammation related genes and immune cell surface markers were detected.Results:(1)Bioinformatics analysis showed that cold stimulation mainly changed the signaling pathways of lipid metabolism and immune system.Flow cytometry analysis showed that the proportion of B lymphocytes in BAT decreased after cold stimulation.(2)CXCL13 expression was significantly increased in BAT and SAT under cold stimulation.(3)CXCL13 expression was significantly increased during the induction and differentiation of primary brown and subcutaneous white adipocytes.(4)CXCL13 promoted thermogenic gene expression in brown adipocytes and might have an effect on macrophage polarization by down-regulating the expression of pro-inflammatory genes in M1 macrophages and up-regulating the marker genes of M2 macrophages.(5)CXCL13 increased the expression of thermogenic genes,affected the expression of Il10 and Tnfα and could increase the expression of the immune cell surface genes in BAT of the mice.Conclusion:(1)The expression of CXCL13 in adipose tissues can be induced by cold stimulation.(2)CXCL13 may play a role in thermogenesis and anti-inflammation in adipose tissues.