MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue
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MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue. / Yadav, Manoj Kumar; Ishida, Megumi; Gogoleva, Natalia; Liao, Ching Wei; Salim, Filiani Natalia; Kanai, Maho; Kuno, Akihiro; Hayashi, Takuto; Shahri, Zeynab Javanfekr; Kulathunga, Kaushalya; Samir, Omar; Lyu, Wenxin; Olivia, Olivia; Mbanefo, Evaristus C.; Takahashi, Satoru; Hamada, Michito.
In: Cell Reports, Vol. 43, No. 4, 113978, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - MAFB in macrophages regulates cold-induced neuronal density in brown adipose tissue
AU - Yadav, Manoj Kumar
AU - Ishida, Megumi
AU - Gogoleva, Natalia
AU - Liao, Ching Wei
AU - Salim, Filiani Natalia
AU - Kanai, Maho
AU - Kuno, Akihiro
AU - Hayashi, Takuto
AU - Shahri, Zeynab Javanfekr
AU - Kulathunga, Kaushalya
AU - Samir, Omar
AU - Lyu, Wenxin
AU - Olivia, Olivia
AU - Mbanefo, Evaristus C.
AU - Takahashi, Satoru
AU - Hamada, Michito
N1 - Publisher Copyright: © 2024 The Author(s)
PY - 2024
Y1 - 2024
N2 - 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/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 Mafbf/f::LysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure.
AB - 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/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 Mafbf/f::LysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure.
KW - BAT
KW - brown adipose tissue thermogenesis
KW - CP: Immunology
KW - CP: Metabolism
KW - interleukin-6 (IL-6)
KW - MAFB
KW - nerve growth factor
KW - NGF
KW - progenitors of brown adipocytes
KW - SN
KW - sympathetic neuronal density
KW - TRPV1+ vascular smooth muscle cells
U2 - 10.1016/j.celrep.2024.113978
DO - 10.1016/j.celrep.2024.113978
M3 - Journal article
C2 - 38522069
AN - SCOPUS:85188521757
VL - 43
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 4
M1 - 113978
ER -
ID: 388041709