000 02347 am a22003733u 4500
042 _adc
100 1 0 _aImbernon, Monica
_eauthor
700 1 0 _aSaponaro, Chiara
_eauthor
_91462
700 1 0 _aHelms, Hans Christian Cederberg
_eauthor
_91463
700 1 0 _aDuquenne, Manon
_eauthor
_91464
700 1 0 _aFernandois, Daniela
_eauthor
_91465
700 1 0 _aDeligia, Eleonora
_eauthor
_91466
700 1 0 _aDenis, Raphael G.P.
_eauthor
_91467
700 1 0 _aChao, Daniela Herrera Moro
_eauthor
_91468
700 1 0 _aRasika, S.
_eauthor
700 1 0 _aStaels, Bart
_eauthor
_91470
700 1 0 _aPattou, François
_eauthor
_91471
700 1 0 _aPfrieger, Frank W.
_eauthor
_91472
700 1 0 _aBrodin, Birger
_eauthor
_91473
700 1 0 _aLuquet, Serge
_eauthor
_91474
700 1 0 _aBonner, Caroline
_eauthor
_91475
700 1 0 _aPrevot, Vincent
_eauthor
245 0 0 _aTanycytes Control Hypothalamic Liraglutide Uptake and its Anti-Obesity Actions
260 _c2022-07-05.
500 _a/pmc/articles/PMC7613793/
500 _a/pubmed/35716660
520 _aLiraglutide, 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.
540 _a
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nCell Metab
856 4 1 _uhttp://dx.doi.org/10.1016/j.cmet.2022.06.002
_zConnect to this object online.
999 _c1953
_d1953