Open AccessThe involvement of 4‐1 BB /4‐1 BBL signaling in glial cell‐mediated hypothalamic inflammation in obesity
Author(s) -
Kim Jiye,
Kwon YoonHee,
Kim ChuSook,
Tu Thai H.,
Kim ByungSam,
Joe Yeonsoo,
Chung Hun T.,
Goto Tsuyoshi,
Kawada Teruo,
Park Taesun,
Choi MyungSook,
Kim MinSeon,
Yu Rina
Publication year - 2018
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12426
Subject(s) - microglia , inflammation , tumor necrosis factor alpha , receptor , astrocyte , biology , immunology , microbiology and biotechnology , endocrinology , central nervous system , biochemistry
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 4‐1 BB /4‐1 BBL between lipid‐laden astrocytes/microglia promotes hypothalamic inflammation in obesity. Stimulation of 4‐1 BB , a member of the TNF receptor superfamily, and/or its ligand 4‐1 BBL 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 4‐1 BB /4‐1 BBL interaction reduced the inflammatory response. Moreover, deficiency of 4‐1 BB reduced hypothalamic inflammation in obese mice fed an high‐fat diet. These findings suggest that 4‐1 BBL /4‐1 BB signaling enhances the glial cell‐mediated inflammatory cross talk and participates in obesity‐induced hypothalamic inflammation.