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/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.
Subject(s)
Adipose Tissue, Brown , Cold Temperature , Interleukin-6 , Macrophages , MafB Transcription Factor , Neurons , Thermogenesis , Animals , MafB Transcription Factor/metabolism , MafB Transcription Factor/genetics , Adipose Tissue, Brown/metabolism , Mice , Macrophages/metabolism , Neurons/metabolism , Interleukin-6/metabolism , RAW 264.7 Cells , Nerve Growth Factor/metabolism , Energy Metabolism , Male , Mice, Inbred C57BLABSTRACT
The central mountainous area of Japan is affected by air pollutant emissions from nearby countries such as China and Korea. Sharp increases in the consumption of fossil fuels in the early 21st century, associated with rapid industrialization in China, resulted in long-range transport of pollutants from East Asia and increases in the harmful effects of pollution. However, the air pollutants emissions have decreased since 2006, when air pollution countermeasures were implemented in China. Furthermore, climatic patterns during 2008-2013 reduced tropospheric ozone concentrations around Japan. Such major changes in the social and climatic environment may have had a significant impact on forests. To investigate this, long-term forest monitoring data obtained at Buna-daira (1190 m a.s.l.), Buna-zaka (1090 m a.s.l.) and Arimine (1350 m a.s.l.) were analyzed. Buna-daira and Buna-zaka forests face the continental side of Mt. Tateyama in Toyama Prefecture. In both stands, the girth growth rate of Fagus crenata was found to have increased after 2008; however, such a tendency was not detected at Arimine, which is surrounded by mountains. The growth rates of Cryptomeria japonica, a conifer resistant to air pollution, were found to remain unchanged or decrease. Here, regional long-range transport of air pollution (including ozone and sulfur oxide) has been demonstrated to influence mountain forests in Japan. In particular, recent decreases in regional air pollution may be an important factor controlling increases in F. crenata, likely through changes in interspecific relationships between species sensitive to and tolerant of air pollution.
