First Author | Yadav MK | Year | 2024 |
Journal | Cell Rep | Volume | 43 |
Issue | 4 | Pages | 113978 |
PubMed ID | 38522069 | Mgi Jnum | J:348025 |
Mgi Id | MGI:7627933 | Doi | 10.1016/j.celrep.2024.113978 |
Citation | Yadav MK, et al. (2024) MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue. Cell Rep 43(4):113978 |
abstractText | Transcription factor MAFB regulates various homeostatic functions of macrophages. This study explores the role of MAFB in brown adipose tissue (BAT) thermogenesis using macrophage-specific Mafb-deficient (Mafb(f/f)::LysM-Cre) mice. We find that Mafb deficiency in macrophages reduces thermogenesis, energy expenditure, and sympathetic neuron (SN) density in BAT under cold conditions. This phenotype features a proinflammatory environment that is characterized by macrophage/granulocyte accumulation, increases in interleukin-6 (IL-6) production, and IL-6 trans-signaling, which lead to decreases in nerve growth factor (NGF) expression and reduction in SN density in BAT. We confirm MAFB regulation of IL-6 expression using luciferase readout driven by IL-6 promoter in RAW-264.7 macrophage cell lines. Immunohistochemistry shows clustered organization of NGF-producing cells in BAT, which are primarily TRPV1(+) vascular smooth muscle cells, as additionally shown using single-cell RNA sequencing and RT-qPCR of the stromal vascular fraction. Treating Mafb(f/f)::LysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure. |