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Temporal specificity of IL-6 knockout in enhancing the thermogenic capability of brown adipose tissue

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Abstract

Although interleukin-6 (IL-6) has been regarded as a homeostatic regulator of fat metabolism, its role in brown adipose thermogenesis remains to be further clarified. By using wild-type (WT) and IL-6-knockout (KO) mice, this study aims to investigate whether IL-6 regulates the thermogenic capability of brown adipose tissue (BAT) at both young and elderly stages. We demonstrated that IL-6 KO enhances BAT thermogenesis at a young age, as evidenced by the increased mRNA and protein expression levels of thermogenic genes, and the elevated interscapular surface temperature. The IL-6-KO enhancement of BAT thermogenesis is associated with improved respiratory exchange ratio (RER) and glucose homeostasis at young stages. However, these improvements disappear in elderly KO mice, which is likely attributable to the highly increased expression of other inflammatory cytokines, such as Tnfα, Il-1β, and Il-10. Our findings indicate that the lack of IL-6 has a temporal-specific contribution to the promotion of BAT thermogenesis.

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Funding

This work was supported by the grant from the Construction Engineering Special Fund of “Taishan Scholars” (No. 201511023, 201712022), the National Key Research and Development Program of China (2017YFE0129800), Funds of Shandong “Double Tops” Program, the Natural Science Foundation of Shandong Province, China (No. ZR2019MC016), and the Program for Scientific Research Innovation Team of Young Scholar in Colleges and Universities of Shandong Province (2019KJE009).

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Authors and Affiliations

  1. State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai’an, 271018, China

    Mei Dong, Cheng Gao, Yanxin Jia, Weijia Xu, Yan Liu, Xin Wen, Qingxin Liu & Haifang Li

  2. College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, 271018, China

    Hai Lin

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  1. Mei Dong
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  2. Cheng Gao
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  3. Yanxin Jia
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  5. Yan Liu
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  6. Xin Wen
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  7. Qingxin Liu
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Contributions

Mei Dong, Cheng Gao, and Yanxin Jia performed experiments, wrote the manuscript, organized the literature and figures. Weijia Xu, Yan Liu, and Xin Wen performed experiments and contributed to discussion. Haifang Li, Hai Lin, and Qingxin Liu conceived the project, led and supervised the study, and reviewed/edited the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Qingxin Liu, Hai Lin or Haifang Li.

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This manuscript does not contain clinical studies or patient data. The experimental protocol with mice was approved by the Animal Care and Use Committee of Shandong Agricultural University.

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Key points

• IL-6 KO enhances brown fat thermogenesis in young mice.

• IL-6 KO improves RER and glucose homeostasis in young mice.

• The thermogenic and metabolic improvements disappear in elderly IL-6-KO mice.

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Dong, M., Gao, C., Jia, Y. et al. Temporal specificity of IL-6 knockout in enhancing the thermogenic capability of brown adipose tissue. J Physiol Biochem 78, 619–628 (2022). https://doi.org/10.1007/s13105-021-00847-4

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  • DOI: https://doi.org/10.1007/s13105-021-00847-4

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