title: Endogenous GLP1 and GLP1 analogue alter CNS responses to palatable food consumption.
abstract: Glucagon-like peptide-1 (GLP1) affects appetite, supposedly mediated via the central nervous system (CNS). In this study, we investigate whether modulation of CNS responses to palatable food consumption may be a mechanism by which GLP1 contributes to the central regulation of feeding. Using functional MRI, we determined the effects of endogenous GLP1 and treatment with the GLP1 analogue liraglutide on CNS activation to chocolate milk receipt. Study 1 included 20 healthy lean individuals and 20 obese patients with type 2 diabetes (T2DM). Scans were performed on two occasions: during infusion of the GLP1 receptor antagonist exendin 9-39 (blocking actions of endogenous GLP1) and during placebo infusion. Study 2 was a randomised, cross-over intervention study carried out in 20 T2DM patients, comparing treatment with liraglutide to insulin, after 10 days and 12 weeks. Compared with lean individuals, T2DM patients showed reduced activation to chocolate milk in right insula (P = 0.04). In lean individuals, blockade of endogenous GLP1 effects inhibited activation in bilateral insula (P ≤ 0.03). Treatment in T2DM with liraglutide, vs insulin, increased activation to chocolate milk in right insula and caudate nucleus after 10 days (P ≤ 0.03); however, these effects ceased to be significant after 12 weeks. Our findings in healthy lean individuals indicate that endogenous GLP1 is involved in the central regulation of feeding by affecting central responsiveness to palatable food consumption. In obese T2DM, treatment with liraglutide may improve the observed deficit in responsiveness to palatable food, which may contribute to the induction of weight loss observed during treatment. However, no long-term effects of liraglutide were observed.
authors.affiliation: Diabetes Center/Department of Internal MedicineVU University Medical Center, Amsterdam, The Netherlands js.tenkulve@vumc.nl.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Ten Kulve
authors.affiliation: Department of PsychiatryVU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Diabetes Center/Department of Internal MedicineVU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Liselotte
authors.initials: L
authors.lastname: van Bloemendaal
authors.affiliation: Department of RadiologyAcademic Medical Center, Amsterdam, The Netherlands.
authors.forename: Paul F C
authors.initials: PF
authors.lastname: Groot
authors.affiliation: Department of PsychiatryAcademic Medical Center, Amsterdam, The Netherlands University of GroningenUniversity Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
authors.forename: Henricus G
authors.initials: HG
authors.lastname: Ruhé
authors.affiliation: Department of Radiology & Nuclear MedicineVU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Diabetes Center/Department of Internal MedicineVU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Diabetes Center/Department of Internal MedicineVU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ijzerman
mesh_terms: D001066:Appetite; D001786:Blood Glucose; D016022:Case-Control Studies; D002490:Central Nervous System / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004435:Eating / Q000502:physiology*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000502:physiology*; D006801:Humans; D000069450:Liraglutide; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D010446:Peptide Fragments
chemical_list: D001786:Blood Glucose; D010446:Peptide Fragments; C083773:exendin (9-39); D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1
keywords: GLP1; fMRI; obesity; palatable food; type 2 diabetes