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Publication : MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue.

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.
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