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Tanycytes Control Hypothalamic Liraglutide Uptake and its Anti-Obesity Actions (Record no. 1693)

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Personal name Imbernon, Monica
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Title Tanycytes Control Hypothalamic Liraglutide Uptake and its Anti-Obesity Actions
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Date of publication, distribution, etc. 2022-07-05.
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General note /pmc/articles/PMC7613793/
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General note /pubmed/35716660
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Summary, etc. Liraglutide, an anti-diabetic drug and agonist of the glucagon-like peptide 1 receptor (GLP1R), has recently been approved to treat obesity in individuals with or without type-2 diabetes. Despite its extensive metabolic benefits, the mechanism and site of action of liraglutide remain unclear. Here, we demonstrate that liraglutide is shuttled to target cells in the mouse hypothalamus by specialized ependymoglial cells called tanycytes, bypassing the blood-brain barrier. Selectively silencing GLP1R in tanycytes or inhibiting tanycytic transcytosis by botulinum neurotoxin expression not only hampers liraglutide transport into the brain and its activation of target hypothalamic neurons, but also blocks its anti-obesity effects on food intake, body weight and fat mass, and fatty acid oxidation. Collectively, these striking data indicate that the liraglutide-induced activation of hypothalamic neurons and its downstream metabolic effects are mediated by its tanycytic transport into the mediobasal hypothalamus, strengthening the notion of tanycytes as key regulators of metabolic homeostasis.
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Language note en
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Topical term or geographic name as entry element Article
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Personal name Saponaro, Chiara
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9 (RLIN) 1462
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Personal name Helms, Hans Christian Cederberg
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9 (RLIN) 1463
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Personal name Duquenne, Manon
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9 (RLIN) 1464
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Personal name Fernandois, Daniela
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9 (RLIN) 1465
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Personal name Deligia, Eleonora
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9 (RLIN) 1466
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Personal name Denis, Raphael G.P.
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9 (RLIN) 1467
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Personal name Chao, Daniela Herrera Moro
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9 (RLIN) 1468
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Personal name Rasika, S.
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Personal name Staels, Bart
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9 (RLIN) 1470
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Personal name Pattou, François
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9 (RLIN) 1471
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Personal name Pfrieger, Frank W.
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9 (RLIN) 1472
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Personal name Brodin, Birger
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9 (RLIN) 1473
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Personal name Luquet, Serge
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9 (RLIN) 1474
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Personal name Bonner, Caroline
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9 (RLIN) 1475
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Personal name Prevot, Vincent
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Note Cell Metab
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Uniform Resource Identifier <a href="http://dx.doi.org/10.1016/j.cmet.2022.06.002">http://dx.doi.org/10.1016/j.cmet.2022.06.002</a>
Public note Connect to this object online.

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