Immunoglobulin Superfamily Containing Leucine-Rich Repeat (Islr) Participates in IL-6-Mediated Crosstalk between Muscle and Brown Adipose Tissue to Regulate Energy Homeostasis

• Published in: International journal of molecular sciences Vol. 23; no. 17; p. 10008
• Main Authors: Liu, Chang, Liu, Jin, Wang, Tongtong, Su, Yang, Li, Lei, Lan, Miaomiao, Yu, Yingying, Liu, Fan, Xiong, Lei, Wang, Kun, Chen, Meijing, Li, Na, Xu, Qing, Hu, Yue, Jia, Yuxin, Meng, Qingyong
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 02.09.2022; MDPI
• Subjects: Adipocytes; Adipose tissue; Adipose tissue (brown); BAT-muscle cross talk; Body fat; Body temperature; Communication; Crosstalk; Energy; Energy balance; Energy expenditure; Gene expression; Homeostasis; Interleukin 6; Islr; Lipids; Mesenchyme; Metabolic disorders; Mitochondria; mitochondrial function; muscle-derived IL-6; Muscles; Musculoskeletal system; Ndufs2; Nicotinamide adenine dinucleotide; Obesity; Progenitor cells; Rodents; Skeletal muscle; Stem cell transplantation; Stem cells; Therapeutic targets; Thermogenesis; Ubiquinone oxidoreductase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231710008

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.