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)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Glucagon-like Peptide-1; Bitter Taste Receptor; Food-intake; Glucose-homeostasis; Insulin-resistance; Brain; Glycosphingolipids; Secretion; Agonist; Neurons
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2019
Prepublished im Jahr
HGF-Berichtsjahr
2019
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 68,
Heft: 12,
Seiten: 2223-2234
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
American Diabetes Association
Verlagsort
Alexandria, VA.
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502200-001
Förderungen
Copyright
Erfassungsdatum
2019-12-10