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.
Bibliographical noteFunding 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.
© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)