AI Article Synopsis

  • - Liraglutide, an anti-diabetic and obesity treatment drug, works by activating GLP1 receptors but its exact mechanism is still not fully understood.
  • - Recent research shows that specialized cells in the brain called tanycytes help transport liraglutide to the hypothalamus, bypassing the blood-brain barrier.
  • - Disabling GLP1 receptors in tanycytes or interrupting their transport function diminishes liraglutide's effects on reducing food intake, body weight, and enhancing fat metabolism, highlighting the critical role of tanycytes in metabolism.

Article Abstract

Liraglutide, an anti-diabetic drug and agonist of the glucagon-like peptide one 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613793PMC
http://dx.doi.org/10.1016/j.cmet.2022.06.002DOI Listing

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