MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue.
Cell Rep
; 43(4): 113978, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38522069
ABSTRACT
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 (Mafbf/fLysM-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 Mafbf/fLysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Marrom
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Interleucina-6
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Temperatura Baixa
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Termogênese
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Fator de Transcrição MafB
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Macrófagos
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article