TY  - BOOK
AU  - Imbernon,Monica
AU  - Saponaro,Chiara
AU  - Helms,Hans Christian Cederberg
AU  - Duquenne,Manon
AU  - Fernandois,Daniela
AU  - Deligia,Eleonora
AU  - Denis,Raphael G.P.
AU  - Chao,Daniela Herrera Moro
AU  - Rasika,S.
AU  - Staels,Bart
AU  - Pattou,François
AU  - Pfrieger,Frank W.
AU  - Brodin,Birger
AU  - Luquet,Serge
AU  - Bonner,Caroline
AU  - Prevot,Vincent
TI  - Tanycytes Control Hypothalamic Liraglutide Uptake and its Anti-Obesity Actions
PY  - 2022///-07-05
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7613793; /pubmed/35716660
N2  - 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
UR  - http://dx.doi.org/10.1016/j.cmet.2022.06.002
ER  -