NMI Regulates Adipose Adaptive Thermogenesis Through TLR4/IRF3 Signaling to Promote Obesity
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2026
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| author | Ting‐Ting Li Xin‐Yuan Zhao Min Zhang Zhuang‐Feng Weng Xiao‐Ran Guo Ying‐Fang Liu Qiao‐Ping Wang Huan‐Huan Liang |
| author_facet | Ting‐Ting Li Xin‐Yuan Zhao Min Zhang Zhuang‐Feng Weng Xiao‐Ran Guo Ying‐Fang Liu Qiao‐Ping Wang Huan‐Huan Liang Ting‐Ting Li Xin‐Yuan Zhao Min Zhang Zhuang‐Feng Weng Xiao‐Ran Guo Ying‐Fang Liu Qiao‐Ping Wang Huan‐Huan Liang |
| collection | Wiley Open Access |
| contents | NMI Regulates Adipose Adaptive Thermogenesis Through TLR4/IRF3 Signaling to Promote Obesity Ting‐Ting Li Xin‐Yuan Zhao Min Zhang Zhuang‐Feng Weng Xiao‐Ran Guo Ying‐Fang Liu Qiao‐Ping Wang Huan‐Huan Liang Advanced Science ABSTRACT Obesity‐associated inflammation is partly driven by damage‐associated molecular patterns (DAMPs). However, whether and how these molecules directly restrain energy expenditure and thereby exacerbate metabolic dysfunction remains unclear. Here, we identify N‐Myc and STAT interactor (NMI) as a stress‐responsive adipokine that suppresses adaptive thermogenesis. NMI expression and secretion are increased in adipocytes exposed to dietary stress and inflammatory cues. Genetic ablation of Nmi protects mice from diet‐induced obesity (DIO) through enhanced energy expenditure and cold tolerance driven by augmented brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. Mechanistically, adipose tissue‐derived NMI activates TLR4/IRF3 signaling, which transcriptionally represses the core thermogenic regulators PPARα, PGC‐1α, and UCP1. Therapeutically, neutralization of NMI with a monoclonal antibody ameliorates obesity and reduces adipose tissue macrophage infiltration in DIO mice. Together, our findings establish NMI as an adipokine that couples inflammatory signaling with suppressed energy expenditure, highlighting its therapeutic potential for obesity and associated metabolic disorders. 10.1002/advs.75921 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/advs.75921 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_advs_75921 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | NMI Regulates Adipose Adaptive Thermogenesis Through TLR4/IRF3 Signaling to Promote Obesity Ting‐Ting Li Xin‐Yuan Zhao Min Zhang Zhuang‐Feng Weng Xiao‐Ran Guo Ying‐Fang Liu Qiao‐Ping Wang Huan‐Huan Liang Advanced Science NMI Regulates Adipose Adaptive Thermogenesis Through TLR4/IRF3 Signaling to Promote Obesity Ting‐Ting Li Xin‐Yuan Zhao Min Zhang Zhuang‐Feng Weng Xiao‐Ran Guo Ying‐Fang Liu Qiao‐Ping Wang Huan‐Huan Liang Advanced Science ABSTRACT Obesity‐associated inflammation is partly driven by damage‐associated molecular patterns (DAMPs). However, whether and how these molecules directly restrain energy expenditure and thereby exacerbate metabolic dysfunction remains unclear. Here, we identify N‐Myc and STAT interactor (NMI) as a stress‐responsive adipokine that suppresses adaptive thermogenesis. NMI expression and secretion are increased in adipocytes exposed to dietary stress and inflammatory cues. Genetic ablation of Nmi protects mice from diet‐induced obesity (DIO) through enhanced energy expenditure and cold tolerance driven by augmented brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. Mechanistically, adipose tissue‐derived NMI activates TLR4/IRF3 signaling, which transcriptionally represses the core thermogenic regulators PPARα, PGC‐1α, and UCP1. Therapeutically, neutralization of NMI with a monoclonal antibody ameliorates obesity and reduces adipose tissue macrophage infiltration in DIO mice. Together, our findings establish NMI as an adipokine that couples inflammatory signaling with suppressed energy expenditure, highlighting its therapeutic potential for obesity and associated metabolic disorders. 10.1002/advs.75921 http://creativecommons.org/licenses/by/4.0/ |
| title | NMI Regulates Adipose Adaptive Thermogenesis Through TLR4/IRF3 Signaling to Promote Obesity |
| topic | Advanced Science |
| url | https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.75921 |