Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity
- Jeu Park1,
- Jin Young Huh1,
- Jiyoung Oh2,
- Jong In Kim1,
- Sang Mun Han1,
- Kyung Cheul Shin1,
- Yong Geun Jeon1,
- Sung Sik Choe1,
- Jiyoung Park2 and
- Jae Bum Kim1
- 1National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea;
- 2Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, South Korea
- Corresponding author: jaebkim{at}snu.ac.kr
Abstract
In obesity, adipose tissue undergoes dynamic remodeling processes such as adipocyte hypertrophy, hypoxia, immune responses, and adipocyte death. However, whether and how invariant natural killer T (iNKT) cells contribute to adipose tissue remodeling are elusive. In this study, we demonstrate that iNKT cells remove unhealthy adipocytes and stimulate the differentiation of healthy adipocytes. In obese adipose tissue, iNKT cells were abundantly found nearby dead adipocytes. FasL-positive adipose iNKT cells exerted cytotoxic effects to eliminate hypertrophic and pro-inflammatory Fas-positive adipocytes. Furthermore, in vivo adipocyte-lineage tracing mice model showed that activation of iNKT cells by alpha-galactosylceramide promoted adipocyte turnover, eventually leading to potentiation of the insulin-dependent glucose uptake ability in adipose tissue. Collectively, our data propose a novel role of adipose iNKT cells in the regulation of adipocyte turnover in obesity.
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Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.329557.119.
- Received June 7, 2019.
- Accepted October 18, 2019.
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