Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging.
The anorexigenic gut hormones oxyntomodulin (OXM) and glucagon-like peptide-1 (GLP-1) are thought to physiologically regulate appetite and food intake. Using manganese-enhanced magnetic resonance imaging, we have shown distinct patterns of neuronal activation in the hypothalamus in response to intraperitoneal injections into fasted mice of 900 and 5400 nmol/kg OXM or 900 nmol/kg GLP-1. Administration of OXM at either dose resulted in a reduced rate of signal enhancement, reflecting a reduction in neuronal activity, in the arcuate, paraventricular, and supraoptic nuclei of the hypothalamus. Conversely, GLP-1 caused a reduction in signal enhancement in the paraventricular nucleus only and an increase in the ventromedial hypothalamic nucleus. Our data show that these two apparently similar peptides generate distinct patterns of activation within the hypothalamus, suggesting that GLP-1 and OXM may act via different hypothalamic pathways.
Chaudhri
Owais B
OB
Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, London W12 0NN, UK.
Parkinson
James R C
JR
Kuo
Yu-Ting
YT
Druce
Maralyn R
MR
Herlihy
Amy H
AH
Bell
Jimmy D
JD
Dhillo
Waljit S
WS
Stanley
Sarah A
SA
Ghatei
Mohammad A
MA
Bloom
Stephen R
SR
D000818:Animals; D004435:Eating / Q000187:drug effects; D005215:Fasting; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D007267:Injections; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008345:Manganese / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D053772:Oxyntomodulin / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*
D053772:Oxyntomodulin; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D008345:Manganese; D052216:Glucagon-Like Peptide 1