The involvement of 4-1BB/4-1BBL signaling in glial cell-mediated hypothalamic inflammation in obesity

Jiye Kim, Yoon Hee Kwon, Chu Sook Kim, Thai H. Tu, Byung Sam Kim, Yeonsoo Joe, Hun T. Chung, Tsuyoshi Goto, Teruo Kawada, Taesun Park, Myung Sook Choi, Min Seon Kim, Rina Yu

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Obesity-induced inflammation occurs not only in peripheral tissues but also in areas of the central nervous system. Glial cells such as astrocytes and microglia play crucial roles in obesity-related hypothalamic inflammation, leading to the derangement of energy metabolism and neurodegenerative pathologies. Here, we show that the interaction of 4-1BB/4-1BBL between lipid-laden astrocytes/microglia promotes hypothalamic inflammation in obesity. Stimulation of 4-1BB, a member of the TNF receptor superfamily, and/or its ligand 4-1BBL on astrocytes and/or microglia with a specific agonist resulted in activation of the inflammatory signaling pathway and enhanced production of inflammatory mediators. Contact coculture of lipid-laden astrocytes and microglia increased the production of inflammatory mediators, and blockade of the 4-1BB/4-1BBL interaction reduced the inflammatory response. Moreover, deficiency of 4-1BB reduced hypothalamic inflammation in obese mice fed an high-fat diet. These findings suggest that 4-1BBL/4-1BB signaling enhances the glial cell-mediated inflammatory cross talk and participates in obesity-induced hypothalamic inflammation.

Original languageEnglish
Pages (from-to)843-853
Number of pages11
JournalFEBS Open Bio
Issue number5
Publication statusPublished - 2018 May

Bibliographical note

Funding Information:
This work was supported by the SRC program (Center for Food & Nutritional Genomics Research: Grant No. 2015R1A5A6001906) and Priority Research Centers Program (2014R1A6A1030318) of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology.

Publisher Copyright:
© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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