Immunoglobulin Superfamily Containing Leucine-Rich Repeat (Islr) Participates in IL-6-Mediated Crosstalk between Muscle and Brown Adipose Tissue to Regulate Energy Homeostasis.
Immunoglobulin Superfamily Containing Leucine-Rich Repeat (Islr) Participates in IL-6-Mediated Crosstalk between Muscle and Brown Adipose Tissue to Regulate Energy Homeostasis.
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DOI：
10.3390/ijms231710008
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发表时间：
2022-09-02
影响因子：
5.6
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中科院分区：
文献类型：
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棕色脂肪组织（BAT）在功能上与骨骼肌相关，因为这两种组织都起源于共同的祖细胞，但控制肌肉与棕色脂肪通讯的精确机制尚不清楚。该报告表明，含有富含亮氨酸重复序列 (Islr) 的免疫球蛋白超家族（Islr）是间充质基质/干细胞的标志物，对于控制 BAT 线粒体功能和全身能量稳态至关重要。心脏毒素损伤后 BAT 中 Islr 缺失的小鼠导致线粒体功能改善、能量消耗增加和生热作用增强。重要的是，我们发现白介素 6 (IL-6) 作为一种肌因子参与了这一过程。从机制上讲，Islr 与 NADH：泛醌氧化还原酶核心亚基 S2 (Ndufs2) 相互作用，调节 IL-6 信号传导；因此，Islr 起到制动器的作用，阻止 IL-6 促进 BAT 活性。总之，这些发现揭示了一种以前未被认识的由 Islr、Ndufs2 和 IL-6 驱动的肌肉-BAT 串扰调节能量稳态的机制，这可能被用作肥胖症的潜在治疗靶点。
Brown adipose tissue (BAT) is functionally linked to skeletal muscle because both tissues originate from a common progenitor cell, but the precise mechanism controlling muscle-to-brown-fat communication is insufficiently understood. This report demonstrates that the immunoglobulin superfamily containing leucine-rich repeat (Islr), a marker of mesenchymal stromal/stem cells, is critical for the control of BAT mitochondrial function and whole-body energy homeostasis. The mice loss of Islr in BAT after cardiotoxin injury resulted in improved mitochondrial function, increased energy expenditure, and enhanced thermogenesis. Importantly, it was found that interleukin-6 (IL-6), as a myokine, participates in this process. Mechanistically, Islr interacts with NADH: Ubiquinone Oxidoreductase Core Subunit S2 (Ndufs2) to regulate IL-6 signaling; consequently, Islr functions as a brake that prevents IL-6 from promoting BAT activity. Together, these findings reveal a previously unrecognized mechanism for muscle-BAT cross talk driven by Islr, Ndufs2, and IL-6 to regulate energy homeostasis, which may be used as a potential therapeutic target in obesity.
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