The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans
Akila De Silva, Victoria Salem, Christopher J Long, Aidan Makwana, Rexford D Newbould, Eugenii A Rabiner, Mohammad A Ghatei, Stephen R Bloom, Paul M Matthews, John D Beaver, Waljit S Dhillo, Akila De Silva, Victoria Salem, Christopher J Long, Aidan Makwana, Rexford D Newbould, Eugenii A Rabiner, Mohammad A Ghatei, Stephen R Bloom, Paul M Matthews, John D Beaver, Waljit S Dhillo
Abstract
Obesity is a major public health issue worldwide. Understanding how the brain controls appetite offers promising inroads toward new therapies for obesity. Peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) are coreleased postprandially and reduce appetite and inhibit food intake when administered to humans. However, the effects of GLP-1 and the ways in which PYY and GLP-1 act together to modulate brain activity in humans are unknown. Here, we have used functional MRI to determine these effects in healthy, normal-weight human subjects and compared them to those seen physiologically following a meal. We provide a demonstration that the combined administration of PYY(3-36) and GLP-1(7-36 amide) to fasted human subjects leads to similar reductions in subsequent energy intake and brain activity, as observed physiologically following feeding.
Copyright © 2011 Elsevier Inc. All rights reserved.
Figures
References
- Adam T.C.M., Jocken J., Westerterp-Plantenga M.S. Decreased glucagon-like peptide 1 release after weight loss in overweight/obese subjects. Obes. Res. 2005;13:710–716.
- Baicy K., London E.D., Monterosso J., Wong M.L., Delibasi T., Sharma A., Licinio J. Leptin replacement alters brain response to food cues in genetically leptin-deficient adults. Proc. Natl. Acad. Sci. USA. 2007;104:18276–18279.
- Batterham R.L., Cowley M.A., Small C.J., Herzog H., Cohen M.A., Dakin C.L., Wren A.M., Brynes A.E., Low M.J., Ghatei M.A. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002;418:650–654.
- Batterham R.L., ffytche D.H., Rosenthal J.M., Zelaya F.O., Barker G.J., Withers D.J., Williams S.C. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Nature. 2007;450:106–109.
- Beaver J.D., Lawrence A.D., van Ditzhuijzen J., Davis M.H., Woods A., Calder A.J. Individual differences in reward drive predict neural responses to images of food. J. Neurosci. 2006;26:5160–5166.
- Farooqi I.S., Bullmore E., Keogh J., Gillard J., O'Rahilly S., Fletcher P.C. Leptin regulates striatal regions and human eating behavior. Science. 2007;317:1355.
- Fletcher P.C., Napolitano A., Skeggs A., Miller S.R., Delafont B., Cambridge V.C., de Wit S., Nathan P.J., Brooke A., O'Rahilly S. Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum. J. Neurosci. 2010;30:14346–14355.
- King J.A., Wasse L.K., Ewens J., Crystallis K., Emmanuel J., Batterham R.L., Stensel D.J. Differential acylated ghrelin, peptide YY3-36, appetite, and food intake responses to equivalent energy deficits created by exercise and food restriction. J. Clin. Endocrinol. Metab. 2011;96:1114–1121.
- LaBar K.S., Gitelman D.R., Parrish T.B., Kim Y.H., Nobre A.C., Mesulam M.M. Hunger selectively modulates corticolimbic activation to food stimuli in humans. Behav. Neurosci. 2001;115:493–500.
- Malik S., McGlone F., Bedrossian D., Dagher A. Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab. 2008;7:400–409.
- Neary N.M., Small C.J., Druce M.R., Park A.J., Ellis S.M., Semjonous N.M., Dakin C.L., Filipsson K., Wang F., Kent A.S. Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively. Endocrinology. 2005;146:5120–5127.
- Pattinson K.T., Mitsis G.D., Harvey A.K., Jbabdi S., Dirckx S., Mayhew S.D., Rogers R., Tracey I., Wise R.G. Determination of the human brainstem respiratory control network and its cortical connections in vivo using functional and structural imaging. Neuroimage. 2009;44:295–305.
- Rosenbaum M., Sy M., Pavlovich K., Leibel R.L., Hirsch J. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J. Clin. Invest. 2008;118:2583–2591.
- Sloth B., Holst J.J., Flint A., Gregersen N.T., Astrup A. Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects. Am. J. Physiol. Endocrinol. Metab. 2007;292:E1062–E1068.
- Turton M.D., O'Shea D., Gunn I., Beak S.A., Edwards C.M., Meeran K., Choi S.J., Taylor G.M., Heath M.M., Lambert P.D. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996;379:69–72.
- Tziortzi A.C., Searle G.E., Tzimopoulou S., Salinas C., Beaver J.D., Jenkinson M., Laruelle M., Rabiner E.A., Gunn R.N. Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy. Neuroimage. 2011;54:264–277.
- Verdich C., Flint A., Gutzwiller J.P., Näslund E., Beglinger C., Hellström P.M., Long S.J., Morgan L.M., Holst J.J., Astrup A. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J. Clin. Endocrinol. Metab. 2001;86:4382–4389.
Source: PubMed