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FEBS Open Bio. 2018 Apr 19;8(5):843-853. doi: 10.1002/2211-5463.12426. eCollection 2018 May.

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

Author information

1
Department of Food Science and Nutrition University of Ulsan South Korea.
2
Department of Biological Science University of Ulsan South Korea.
3
Graduate School of Agriculture Kyoto University Uji Japan.
4
Department of Food and Nutrition Yonsei University Seoul South Korea.
5
Department of Food Science and Nutrition Center for Food and Nutritional Genomics Research Kyungpook National University Daegu South Korea.
6
Division of Endocrinology and Metabolism University of Ulsan College of Medicine Seoul South Korea.

Abstract

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.

KEYWORDS:

hypothalamus; inflammation; obesity

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