产热
生物
MECP2
脂肪组织
褐色脂肪组织
平衡
白色脂肪组织
细胞生物学
内分泌学
脂肪组织巨噬细胞
内科学
表型
基因
遗传学
医学
作者
Yochai Wolf,Sigalit Boura‐Halfon,Nina Cortese,Zhana Haimon,Hadas Sar Shalom,Yael Kuperman,Vyacheslav Kalchenko,Alexander Brandis,Eyal David,Yifat Segal-Hayoun,Louise Chappell‐Maor,Avraham Yaron,Steffen Jung
摘要
Tissue macrophages provide immunological defense and contribute to the establishment and maintenance of tissue homeostasis. Here we used constitutive and inducible mutagenesis to delete the nuclear transcription regulator Mecp2 in macrophages. Mice that lacked the gene encoding Mecp2, which is associated with Rett syndrome, in macrophages did not show signs of neurodevelopmental disorder but displayed spontaneous obesity, which was linked to impaired function of brown adipose tissue (BAT). Specifically, mutagenesis of a BAT-resident Cx3Cr1+ macrophage subpopulation compromised homeostatic thermogenesis but not acute, cold-induced thermogenesis. Mechanistically, malfunction of BAT in pre-obese mice with mutant macrophages was associated with diminished sympathetic innervation and local titers of norepinephrine, which resulted in lower expression of thermogenic factors by adipocytes. Mutant macrophages overexpressed the signaling receptor and ligand PlexinA4, which might contribute to the phenotype by repulsion of sympathetic axons expressing the transmembrane semaphorin Sema6A. Collectively, we report a previously unappreciated homeostatic role for macrophages in the control of tissue innervation. Disruption of this circuit in BAT resulted in metabolic imbalance.
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