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Herrera Moro Chao, D.* ; Wang, Y.* ; Foppen, E.* ; Ottenhoff, R.* ; van Roomen, C.* ; Parlevliet, E.T.* ; van Eijk, M.J.T.* ; Verhoek, M.* ; Boot, R.* ; Marques, A.R.* ; Scheij, S.* ; Mirzaian, M.* ; Kooijman, S.* ; Jansen, K.* ; Wang, D.* ; Mergen, C. ; Seeley, R.J.* ; Tschöp, M.H. ; Overkleeft, H.* ; Rensen, P.C.N.* ; Kalsbeek, A.* ; Aerts, J.M.F.G.* ; Yi, C.X.*

The iminosugar AMP-DNM improves satiety and activates brown adipose tissue through GLP1.

Diabetes 68, 2223-2234 (2019)
Verlagsversion Postprint DOI
Open Access Green
Obesity is taking on worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar N-adamantine-methyloxypentyl-deoxynojirimycin (AMP-DNM), which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here we show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in obese rodents. Moreover, we demonstrate that the mechanism mediating these favorable actions depends on oral, but not central, administration of AMP-DNM, which ultimately stimulates systemic glucagon-like peptide 1 (GLP1) secretion. We evidence an essential role of brain GLP1 receptors (GLP1r), as AMP-DNM fails to promote satiety and activate BAT in mice lacking the brain GLP1r as well as in mice treated intracerebroventricularly with GLP1r antagonist exendin-9. In conclusion, AMP-DNM markedly ameliorates metabolic abnormalities in obese rodents by restoring satiety and activating BAT through central GLP1r, while improving glucose homeostasis by mechanisms independent of central GLP1r.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Glucagon-like Peptide-1; Bitter Taste Receptor; Food-intake; Glucose-homeostasis; Insulin-resistance; Brain; Glycosphingolipids; Secretion; Agonist; Neurons
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 68, Heft: 12, Seiten: 2223-2234 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)