000 | 02347 am a22003733u 4500 | ||
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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 |
_c1693 _d1693 |