1. CXCL5 secreted from macrophages during cold exposure mediates white adipose tissue browning
- Author
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Dabin Lee, Je-Yoel Cho, Sang-Hyuk Yoon, Yeo-Dae Yoon, Ki-Hoan Nam, A-Reum Nam, Sang-Mi Cho, Dong Wook Kim, and Kang-Hoon Lee
- Subjects
WT, wild type ,Chemokine CXCL5 ,CXCL5, C-X-C motif chemokine ligand 5 ,TNFα, tumor necrosis factor-α ,Adipose tissue ,iWAT ,TW, tissue weight ,White adipose tissue ,Biochemistry ,iWAT, inguinal white adipose tissue ,Mice ,Endocrinology ,Brown adipose tissue ,FASP, filter-aided sample preparation ,EBF2, early B cell factor 2 ,p-CREB, phosphorylated cAMP response element-binding protein ,M1 macrophages ,Cells, Cultured ,PRDM16 ,Mice, Knockout ,BW, body weight ,thermogenesis ,Thermogenin ,Cell biology ,medicine.anatomical_structure ,MGL1, macrophage galactose-type lectin-1 ,EAR2, eosinophil cationic protein 2 ,Tumor necrosis factor alpha ,Research Article ,UCP1 ,PKA, protein kinase cAMP-dependent ,PPARγ, peroxisome proliferator-activated receptor gamma ,Adipose Tissue, White ,Adipokine ,Mice, Transgenic ,QD415-436 ,Biology ,BMDM, bone-marrow-derived monocyte ,C/EBPβ, CCAAT-enhancer-binding protein β ,proteomics ,UCP1, uncoupling protein 1 ,medicine ,Animals ,ELOVL3, elongation of very long chain fatty acids protein 3 ,KO, knockout ,Macrophages ,Cell Biology ,SIRT1, sirtuin1 ,PGC1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha ,BAT, brown adipose tissue ,COX8b, cytochrome c oxidase subunit 8B ,Mice, Inbred C57BL ,CIDEA, cell-death-inducing DFFA-like effector A ,KO mouse ,cold stress ,PRDM16, PR/SET domain 16 ,beta-adrenergic signaling ,Thermogenesis ,M1 macrophage - Abstract
Adipose tissue affects metabolic-related diseases because it consists of various cell types involved in fat metabolism and adipokine release. CXC ligand 5 (CXCL5) is a member of the CXC chemokine family and is highly expressed by macrophages in white adipose tissue (WAT). In this study, we generated and investigated the function of CXCL5 in knockout (KO) mice using CRISPR/Cas9. The male KO mice did not show significant phenotype differences in normal conditions. However, proteomic analysis revealed that many proteins involved in fatty acid beta-oxidation and mitochondrial localization were enriched in the inguinal WAT (iWAT) of Cxcl5 KO mice. Cxcl5 KO mice also showed decreased protein and transcript expression of genes associated with thermogenesis, including uncoupling protein 1 (UCP1), a well-known thermogenic gene, and increased expression of genes associated with inflammation. The increase in UCP1 expression in cold conditions was significantly retarded in Cxcl5 KO mice. Finally, we found that CXCL5 treatment increased the expression of transcription factors that mediate Ucp1 expression and Ucp1 itself. Collectively, our data show that Ucp1 expression is induced in adipocytes by CXCL5, which is secreted upon β-adrenergic stimulation by cold stimulation in M1 macrophages. Our data indicate that CXCL5 plays a crucial role in regulating energy metabolism, particularly upon cold exposure. These results strongly suggest that targeting CXCL5 could be a potential therapeutic strategy for people suffering from disorders affecting energy metabolism.
- Published
- 2021