脂肪组织
促炎细胞因子
生物
葡萄糖稳态
炎症
能量稳态
下调和上调
内分泌学
转录因子
脂肪组织巨噬细胞
内科学
细胞生物学
白色脂肪组织
免疫学
胰岛素抵抗
医学
胰岛素
基因
生物化学
肥胖
作者
Yuta Hiraike,Kaede Saito,Misato Oguchi,Takahito Wada,Gotaro Toda,Seiichiro Tsutsumi,Kana Bando,Junji Sagawa,Gaku Nagano,Haruya Ohno,Naoto Kubota,Tetsuya Kubota,Hiroyuki Aburatani,Takashi Kadowaki,Hironori Waki,Shintaro Yanagimoto,Toshimasa Yamauchi
标识
DOI:10.1073/pnas.2308750120
摘要
Adipose tissue is central to regulation of energy homeostasis. Adaptive thermogenesis, which relies on mitochondrial oxidative phosphorylation (Ox-Phos), dissipates energy to counteract obesity. On the other hand, chronic inflammation in adipose tissue is linked to type 2 diabetes and obesity. Here, we show that nuclear factor I-A (NFIA), a transcriptional regulator of brown and beige adipocytes, improves glucose homeostasis by upregulation of Ox-Phos and reciprocal downregulation of inflammation. Mice with transgenic expression of NFIA in adipocytes exhibited improved glucose tolerance and limited weight gain. NFIA up-regulates Ox-Phos and brown-fat-specific genes by enhancer activation that involves facilitated genomic binding of PPARγ. In contrast, NFIA in adipocytes, but not in macrophages, down-regulates proinflammatory cytokine genes to ameliorate adipose tissue inflammation. NFIA binds to regulatory region of the Ccl2 gene, which encodes proinflammatory cytokine MCP-1 (monocyte chemoattractant protein-1), to down-regulate its transcription. CCL2 expression was negatively correlated with NFIA expression in human adipose tissue. These results reveal the beneficial effect of NFIA on glucose and body weight homeostasis and also highlight previously unappreciated role of NFIA in suppressing adipose tissue inflammation.
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