期刊
INTERNATIONAL JOURNAL OF OBESITY
卷 40, 期 11, 页码 1699-1706出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ijo.2016.121
关键词
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资金
- University of Copenhagen
- Danish Council for Independent Research, Denmark [DFF-4092-00218]
- Copenhagen University Hospital Hvidovre, Denmark
- Danish Medical Association, Denmark
- NNF Center for Basic Metabolic Research [Holst Group] Funding Source: researchfish
BACKGROUND/OBJECTIVES: Exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) may explain appetite reduction and weight loss after Roux-en-Y gastric bypass (RYGB), but causality has not been established. We hypothesized that food intake decreases after surgery through combined actions from GLP-1 and PYY. GLP-1 actions can be blocked using the GLP-1 receptor antagonist Exendin 9-39 (Ex-9), whereas PYY actions can be inhibited by the administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor preventing the formation of PYY3-36. SUBJECTS/METHODS: Appetite-regulating gut hormones and appetite ratings during a standard mixed-meal test and effects on subsequent ad libitum food intake were evaluated in two studies: in study 1, nine patients with type 2 diabetes were examined prospectively before and 3 months after RYGB with and without Ex-9. In study 2, 12 RYGB-operated patients were examined in a randomized, placebo-controlled, crossover design on four experimental days with: (1) placebo, (2) Ex-9, (3) the DPP-4 inhibitor, sitagliptin, to reduce formation of PYY3-36 and (4) Ex-9/sitagliptin combined. RESULTS: In study 1, food intake decreased by 35% following RYGB compared with before surgery. Before surgery, GLP-1 receptor blockage increased food intake but no effect was seen postoperatively, whereas PYY secretion was markedly increased. In study 2, combined GLP-1 receptor blockage and DPP-4 inhibitor mediated lowering of PYY3-36 increased food intake by similar to 20% in RYGB patients, whereas neither GLP-1 receptor blockage nor DPP-4 inhibition alone affected food intake, perhaps because of concomitant marked increases in the unblocked hormone. CONCLUSIONS: Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY3-36, resulted in concomitant increased secretion of the other, probably explaining the absent effect on food intake on these experimental days. Combined blockade of GLP-1 and PYY actions increased food intake after RYGB, supporting that these hormones have a role in decreased food intake postoperatively.
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