Abstract
OBJECTIVE: It has been suggested that weight reduction and improvements in satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite and weight reduction, mediated via effects on the central nervous system (CNS). Secretion of GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS.
RESEARCH DESIGN AND METHODS: Effects of the GLP-1 receptor antagonist exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after RYGB. We used functional MRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk), comparing results with Ex9-39 versus placebo before and after RYGB.
RESULTS: After RYGB, CNS activation was reduced in the rolandic operculum and caudate nucleus in response to viewing food pictures (P= 0.03) and in the insula in response to consumption of palatable food (P= 0.003). GLP-1 levels were significantly elevated postoperatively (P< 0.001). After RYGB, GLP-1 receptor blockade resulted in a larger increase in activation in the caudate nucleus in response to food pictures (P= 0.02) and in the insula in response to palatable food consumption (P= 0.002).
CONCLUSIONS: We conclude that the effects of RYGB on CNS activation in response to visual and gustatory food cues may be mediated by central effects of GLP-1. Our findings provide further insights into the mechanisms underlying the weight-lowering effects of RYGB.
Original language | English |
---|---|
Pages (from-to) | 1522-1529 |
Number of pages | 8 |
Journal | Diabetes Care |
Volume | 40 |
Issue number | 11 |
Early online date | 12 Oct 2017 |
DOIs | |
Publication status | Published - 1 Nov 2017 |
Funding
Gassman (Department of Internal Medicine, VU University Medical Center) and Ton Schweigmann (Department of Radiology and Nuclear Medicine, VU University Medical Center) for their assistance during the test visits, as well as the subjects who participated in this study. The authors thank Nutricia for providing the Nutridrink. Funding. R.G.I. is financed by the Netherlands Organisation for Scientific Research (NWO) Innovational Research Incentives Scheme Veni (no. 91613082). DualityofInterest.C.F.D.hasreceivedconsultancy/ speaker fees from Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, and Novo Nordisk. J.J.H. has received fees for consulting, lecturing, and/or being part of an advisory board from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, GI Dynamics, Merck Sharp & Dohme, Novo Nordisk, Novartis, Sanofi, Takeda, and Zealand Pharma. M.D. was a consultant for Abbott, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly and Company, GI Dynamics, Merck Sharp & Dohme, Novo Nordisk, Poxel SA, and Sanofi and was a speaker for Bristol-Myers Squibb/AstraZeneca, Eli Lilly and Company, Novo Nordisk, and Sanofi. Through M.D., the VU University Medical Center received research grants from Abbott, Bristol-Myers Squibb/ AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme, Novo Nordisk, and Sanofi. R.G.I. is the principal investigator of studies sponsored by research grants from Novo Nordisk and Eli Lilly and Company. M.D. and R.G.I. report receiving no personal payments in connection to the above-mentioned activities, but all payments were directly transferred to the Diabetes Center (VU University Medical Center) nonprofit research foundation. No other potential conflicts of interest relevant to this article were reported. Author Contributions. J.S.t.K. designed the study, conducted the experiments, designed the fMRI paradigm, performed data analysis, and wrote the manuscript. D.J.V. designed the fMRI paradigm, performeddataanalysis,andwrotethemanuscript. V.E.A.G. contributed to the design and the performance of the study and contributed to writing the manuscript. L.v.B. designed the fMRI paradigm and contributed to writing the manuscript. F.B. performed analyses of all structural MRI scans and contributed to writing the manuscript. C.F.D. and J.J.H. performed laboratory analyses and contributed to writing the manuscript. M.L.D. contributed to the design of the study and to writing the manuscript. M.D. designed the study. R.G.I. designed the study, performed data analysis,andwrotethemanuscript.Allauthorshave seen and approved the final version of the manuscript. J.S.t.K. and R.G.I. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Keywords
- Journal Article