Differential responses of circulating amylin to high-fat vs. high-carbohydrate meal in healthy men
Lindsay K. Eller,
Philip N. Ainslie, Marc J. Poulin,
Raylene A. Reimer,
Lindsay K. Eller
Departments of Physiology and Biophysics,
Faculties of Medicine and Kinesiology,
Search for more papers by this authorMarc J. Poulin
Departments of Physiology and Biophysics,
Clinical Neurosciences and
Faculties of Medicine and Kinesiology,
Hotchkiss Brain Institute and
Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada
Search for more papers by this authorRaylene A. Reimer
Biochemistry and Molecular Biology,
Faculties of Medicine and Kinesiology,
Search for more papers by this authorLindsay K. Eller,
Philip N. Ainslie, Marc J. Poulin,
Raylene A. Reimer,
Lindsay K. Eller
Departments of Physiology and Biophysics,
Faculties of Medicine and Kinesiology,
Search for more papers by this authorMarc J. Poulin
Departments of Physiology and Biophysics,
Clinical Neurosciences and
Faculties of Medicine and Kinesiology,
Hotchkiss Brain Institute and
Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada
Search for more papers by this authorRaylene A. Reimer
Biochemistry and Molecular Biology,
Faculties of Medicine and Kinesiology,
Search for more papers by this author Dr Raylene Reimer, Faculties of Kinesiology and Medicine, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada. Tel.: +1(403) 220 8218; Fax: +1(403) 284 3553; E-mail: [email protected]
Summary
Objective The success of an amylin analogue in weight loss trials has generated interest in amylin as a physiological satiety signal. Little is known about how plasma amylin responds to macronutrients. This study examined the effects of a high-carbohydrate meal (CHO), a high-fat meal (FAT) or a continued fast (FAST) on amylin concentrations and correlations among other satiety hormones and measures of appetite.
Design/patients In a randomized, crossover design, 10 healthy males consumed a meal high in carbohydrate or fat or continued fasted.
Measurements Blood samples and subjective hunger scores were obtained at baseline and 30, 90 and 210 min postprandial.
Results After CHO, amylin, insulin and C-peptide were greater and des-acyl ghrelin lower compared to FAT (P < 0·001). Area under the curve (AUC) was greater for amylin and insulin and lower for des-acyl ghrelin following CHO. Subjective satiety and fullness were higher for CHO and FAT than FAST at 30 and 90 min but only for CHO at 210 min (P < 0·01). Hunger and desire to eat were lower for CHO and FAT than FAST at 30 and 90 min but only for CHO at 210 min (P < 0·005). Amylin was negatively correlated to hunger, desire to eat, and nausea and positively related to satiety and insulin. Des-acyl ghrelin was negatively associated with C-peptide, insulin and GLP-1 and satiety.
Conclusions CHO enhances amylin and suppresses des-acyl ghrelin to a greater extent than FAT in healthy men. The mechanisms responsible for these changes and their implications in the physiology of satiety remain to be elucidated.
References
- 1 Badman, M.K. & Flier, J.S. (2005) The gut and energy balance: visceral allies in the obesity wars. Science, 307, 1909–1914.
- 2 Huda, M.S.B., Wilding, J.P.H. & Pinkney, J.H. (2006) Gut peptides and the regulation of appetite. Obesity Reviews, 7, 163–182.
- 3 Woods, S.C., Lutz, T.A., Geary, N. & Langhans, W. (2006) Pancreatic signals controlling food intake: insulin, glucagon and amylin. Philosophical Transactions of the Royal Society of London, Series B. Biological Sciences, 361, 1219–1235.
- 4 Flint, A., Raben, A., Astrup, A. & Holst, J.J. (1998) Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. Journal of Clinical Investigation, 101, 515–520.
- 5 Naslund, E., Barkeling, B., King, N., Gutniak, M., Blundell, J.E., Holst, J.J., Rössner, S. & Hellström, P.M. (1999) Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. International Journal of Obesity and Related Metabolic Disorders, 23, 304–311.
- 6 Wren, A.M., Seal, L.J., Cohen, M.A., Brynes, A.E., Frost, G.S., Murphy, K.G., Dhillo, W.S., Ghatei, M.A. & Bloom, S.R. (2001) Ghrelin enhances appetite and increases food intake in humans. Journal of Clinical Endocrinology and Metabolism, 86, 5992–5995.
- 7 Kreymann, B., Williams, G., Ghatei, M.A. & Bloom, S.R. (1987) Glucagon-like peptide-1, 7–36: a physiological incretin in man. Lancet, 2, 1300–1304.
- 8 Eissele, R., Goke, R., Willemer, S., Harthus, H.P., Vermeer, H., Arnold, R. & Goke, B. (1992) Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. European Journal of Clinical Investigation, 22, 283–191.
- 9 Drucker, D.J. (2006) The biology of incretin hormones. Cell Metabolism, 3, 153–165.
- 10 Toshinai, K., Mondal, M.S., Nakazato, M., Date, Y., Murakami, N., Kojima, M., Kangawa, K. & Matsukura, S. (2001) Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypglycemia, and leptin administration. Biochemical and Biophysical Research Communications, 281, 1220–1225.
- 11 Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H. & Kangawa, K. (1999) Ghrelin is a growth-hormone-releasing acylate peptide from stomach. Nature, 402, 656–660.
- 12 Tschop, M., Wawarta, R., Riepl, R.L., Friedrich, S., Bidlingmaier, M., Landgraf, R. & Folwaczny, C. (2001) Post-prandial decrease of circulating human ghrelin levels. Journal of Clinical Investigation, 24, RC19–RC21.
- 13 Overduin, J., Frayo, R.S., Grill, H.J., Kaplan, J.M. & Cummings, D.E. (2005) Role of the duodenum and macronutrient type in ghrelin regulation. Endocrinology, 146, 845–850.
- 14 Hosoda, H., Kojima, M., Matsuo, H. & Kangawa, K. (2000) Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochemical and Biophysical Research Communications, 279, 909–913.
- 15 Van Der Lely, A.J., Tschop, M., Heiman, M.L. & Ghigo, E. (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocrine Reviews, 25, 426–457.
- 16 Asakawa, A., Inui, A., Fujimiya, M., Sakamaki, R., Shinfuku, N., Ueta, Y., Meguid, M.M. & Kasuga, M. (2005) Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut, 54, 18–24.
- 17 Chen, C.-Y., Inui, A., Asakawa, A., Fujino, K., Kato, I., Chen, C.-C., Ueno, N. & Fujimiya, M. (2005) Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology, 129, 8–25.
- 18 Chen, C.Y., Chao, Y., Chang, F.Y., Chien, E.J., Lee, S.D. & Doong, M.L. (2005) Intracisternal des-acyl ghrelin inhibits food intake and non-nutrient gastric emptying in conscious rats. International Journal of Molecular Medicine, 16, 695–699.
- 19 Lutz, T.A. (2006) Amylinergic control of food intake. Physiology and Behavior, 89, 465–471.
- 20 Schwartz, M.W., Woods, S.C., Porte, D. Jr, Seeley, R.J. & Baskin, D.G. (2000) Central nervous system control of food intake. Nature, 404, 661–671.
- 21 Xu, A.W., Kaelin, C.B., Takeda, K., Akira, S., Schwartz, M.W. & Barsh, G.S. (2005) PI3K integrates the action of insulin and leptin on hypothalamic neurons. Journal of Clinical Investigation, 115, 951–958.
- 22 Riediger, T., Schmid, H.A., Lutz, T.A. & Simon, E. (2002) Amylin and glucose co-activate area postrema neurons of the rat. Neuroscience Letters, 328, 121–124.
- 23 Smith, S.R., Blundell, J., Burns, C., Ellero, C., Schroeder, B.E., Kesty, N.C., Chen, K., Halseth, A.E., Lush, C.W. & Weyer, C. (2007) Pramlintide treatment reduces 24-hour caloric intake and meal sizes, and improves control of eating in obese subjects: a 6-week translational research study. American Journal of Physiology. Endocrinology and Metabolism, 293, E620–E627.
- 24 Chapman, I., Parker, B., Doran, S., Feinle-Bisset, C., Wishart, J., Lush, C.W., Chen, K., Lacerte, C., Burns, C., McKay, R., Weyer, C. & Horowitz, M. (2007) Low-dose pramlinitide reduced food intake and meal duration in healthy, normal-weight subjects. Obesity (Silver Spring), 15, 1179–1186.
- 25 Aronne, L., Fujioka, K., Aroda, V., Chen, K., Halseth, A., Kesty, N.C., Burns, C., Lush, C.W. & Weyer, C. (2007) Progressive reduction in body weight following treatment with the amylin analog pramlinitide in obese subjects: a phase 2, randomized, placebo-controlled, dose-education study. Journal of Clinical Endocrinology and Metabolism, 92, 2977–2983.
- 26 Rushing, P.A., Hagan, M.M., Seeley, R.J., Lutz, T.A., D’Alessio, D.A., Air, E.L. & Woods, S.C. (2001) Inhibition of central amylin signaling increases food intake and body adiposity in rats. Endocrinology, 142, 5035–5038.
- 27 Reidelberger, R.D., Haver, A.C., Arnelo, U., Smith, D.D., Schaffert, C.S. & Permert, J. (2004) Amylin receptor blockade stimulates food intake in rats. American Journal of Physiology, 287, R568–R574.
- 28 Osto, M., Wielinga, P.Y., Alder, B., Walser, N. & Lutz, T.A. (2007) Modulation of the satiating effect of amylin by central ghrelin, leptin and insulin. Physiology and Behavior, 91, 566–572.
- 29 Anderson, G.H., Aziz, A. & Abou Samra, R. (2006) Physiology of food intake regulation: interaction with dietary components. Nestle Nutrition Workshop Series: Pediatric Program, 58, 133–143.
- 30 Orr, J. & Davy, B. (2005) Dietary influences on peripheral hormones regulating energy intake: potential applications for weight management. Journal of the American Dietetic Association, 105, 1115–1124.
- 31 Stubbs, J., Ferres, S. & Horgan, G. (2000) Energy density of foods: effects on energy intake. Critical Reviews in Food Science and Nutrition, 40, 481–515.
- 32 Flint, A., Raben, A., Blundell, J.E. & Astrup, A. (2000) Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. International Journal of Obesity and Related Metabolic Disorders, 24, 38–48.
- 33 Raben, A., Tagliabue, A. & Astrup, A. (1995) The reproducibility of subjective appetite scores. British Journal of Nutrition, 73, 517–530.
- 34 Stubbs, R.J., Hughes, D.A., Johnstone, A.M., Rowley, E., Reid, C., Elia, M., Stratton, R., Delargy, H., King, N. & Blundell, J.E. (2000) The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. British Journal of Nutrition, 84, 405–415.
- 35 Sepple, C.P. & Read, N.W. (1989) Gastrointestinal correlates of the development of hunger in man. Appetite, 13, 183–191.
- 36 Pruessner, J.C., Kirschbaum, C., Meinlschmid, G. & Hellhammer, D.H. (2003) Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology, 28, 916–931.
- 37 Lutz, T.A. (2005) Pancreatic amylin as a centrally acting satiating hormone. Current Drug Targets, 6, 181–189.
- 38 Butler, P.C., Chou, J., Carter, W.B., Wang, Y.N., Bu, B.H., Chang, D., Chang, J.K. & Rizza, R.A. (1990) Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans. Diabetes, 39, 752–756.
- 39 Rachman, J., Payne, M.J., Levy, J.C., Barrow, B.A., Holman, R.R. & Turner, R.C. (1998) Changes in amylin and amylin-like peptide concentrations and beta-cell function in response to sulfonylurea or insulin therapy in NIDDM. Diabetes Care, 21, 810–816.
- 40 Ludvik, B., Lell, B., Hartter, E., Schnack, C. & Prager, R. (1991) Decrease of stimulated plasma levels of pancreatic amylin indicates its cosecretion with insulin in humans. Diabetes, 40, 1615–1619.
- 41 Roth, J.D., Hughes, H., Kendall, E., Baron, A.D. & Anderson, C.M. (2006) Antiobesity effects of the B-cell hormone amylin in diet-induced obese rats: effects on food intake, body weight, composition, energy expenditure, and gene expression. Endocrinology, 147, 5855–5864.
- 42 Sanke, T., Hanabusa, T., Nakanao, Y., Oki, C., Okai, K., Nishimura, S., Kondo, M. & Nanjo, K. (1991) Plasma islet amyloid polypeptide (amylin) levels and their responses to oral glucose in type 2 (non-insulin-dependent) diabetic patients. Diabetologia, 34, 129–132.
- 43 Monteleone, P., Bencivenga, R., Longobardi, N., Serritella, C. & Maj, M. (2003) Differential responses of circulating ghrelin to high-fat or high-carbohydrate meal in healthy women. Journal of Clinical Endocrinology and Metabolism, 88, 5510–5514.
- 44 Romon, M., Gomila, S., Hinicker, P., Soudan, B. & Dallongeville, J. (2006) Influence of weight loss on plasma ghrelin responses to high-fat and high-carbohydrate test meals in obese women. Journal of Clinical Endocrinology and Metabolism, 91, 1034–1041.
- 45 Reid, M. & Hetherington, M. (1997) Relative effects of carbohydrates and protein on satiety: a review of methodology. Neuroscience Biobehavior Reviews, 21, 295–308.
- 46 Flint, A., Moller, B.K., Raben, A., Sloth, B., Pedersen, D., Tetens, I., Holst, J.J. & Astrup, A. (2006) Glycemic and insulinemic responses as determinants of appetite in humans. American Journal of Clinical Nutrition, 84, 1365–1373.
- 47 Blom, W.A.M., Stafleu, A., De Graaf, C., Kok, F.J., Schaafsma, G. & Hendriks, H.F.J. (2005) Ghrelin response to carbohydrate-enriched breakfast is related to insulin. American Journal of Clinical Nutrition, 81, 367–375.
- 48 Hagemann, D., Holst, J.J., Gethmann, A., Banasch, M., Schmidt, W.E. & Meier, J.J. (2007) Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased insulin secretion. Regulatory Peptides, 143, 64–68.
- 49 Michel, S., Becskei, C., Erguven, E., Lutz, T.A. & Riediger, T. (2007) Diet-derived nutrients modulate the effects of amylin on c-fos expression in the area postrema and on food intake. Neuroendocrinology, 86, 124–135.
- 50 Ariyasu, H., Takaya, K., Tagami, T., Ogawa, Y., Hosoda, H., Akamizu, T., Suda, M., Koh, T., Natsui, K., Toyooka, S., Shirakami, G., Usui, T., Shimatsu, A., Doi, K., Hosoda, H., Kojima, M., Kangawa, K. & Nakao, K. (2001) Stomach is a major source of circulating ghrelin and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. Journal of Clinical Endocrinology and Metabolism, 86, 4573–4578.
- 51 Weigle, D.S., Cummings, D.E., Newby, P.D., Breen, P.A., Frayo, R.S., Matthys, C., Callahan, H.S. & Purnell, J.Q. (2003) Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet. Journal of Clinical Endocrinology and Metabolism, 88, 1577–1586.
- 52 Gil-Campos, M., Aguilera, C.M., Canete, R. & Gil, A. (2006) Ghrelin: a hormone regulating food intake and energy homeostasis. British Journal of Nutrition, 96, 201–226.
- 53 Higgins, S.C., Gueorquiev, M. & Korbonits, M. (2007) Ghrelin, the peripheral hunger hormone. Annals of Medicine, 39, 116–136.
- 54 Toshinai, K., Yamaguchi, H., Sun, Y., Smith, R.G., Yamanaka, A., Sakurai, T., Date, Y., Mondal, M.S., Shimbara, T., Kawagoe, T., Murakami, N., Miyazato, M., Kangawa, K. & Nakazato, M. (2006) Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology, 147, 2306–2314.
- 55 Neary, N.M., Druce, M.R., Small, C.J. & Bloom, S.R. (2005) Acylated ghrelin stimulates food intake in the fed and fasted states but desacylated ghrelin has no effect. Gut, 55, 135.
- 56 Ello-Martin, J.A., Ledikwe, J.H. & Rolls, B.J. (2005) The influence of food portion size and energy density on energy intake: implications for weight management. American Journal of Clinical Nutrition, 82 (Suppl.), 236S–241S.
- 57 Kral, T.V.E. & Rolls, B.J. (2004) Energy density and portion size: their independent and combined effects on energy intake. Physiology and Behavior, 82, 131–138.
- 58 Vincent, R., Roberts, A., Frier, M., Perkins, A.C., Macdonald, I.A. & Spiller, R.C. (1995) Effect of bran particle size on gastric emptying and small bowel transit in humans: a scintigraphic study. Gut, 37, 216–219.
- 59 Gelbiebter, A., Melton, P.M., McCray, R.S., Gallagher, D.R., Gage, D. & Hashim, S.A. (1992) Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women. American Journal of Clinical Nutrition, 56, 656–661.
- 60 In Park, M., Camilleri, M., O’Connor, H., Oenning, L., Burton, D., Stephens, D. & Zinsmeister, A.R. (2007) Effect of different macronutrients in excess on gastric sensory and motor functions and appetite in normal-weight, overweight and obese humans. American Journal of Clinical Nutrition, 85, 411–418.
- 61 Chaudhri, O., Small, C. & Bloom, S. (2006) Gastrointestinal hormones regulating appetite. Philosophical Transactions of the Royal Society of London, Series B. Biological Sciences, 361, 1187–1209.
- 62 Hollander, P., Maggs, D.G., Ruggles, J.A., Fineman, M., Shen, L., Kolterman, O.G. & Weyer, C. (2004) Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obesity Research, 12, 661–668.
- 63 Chapman, I., Parker, B., Doran, S., Feinle-Bisset, C., Wishart, J., Strobel, S., Wang, Y., Burns, C., Lush, C., Weyer, C. & Horowitz, M. (2005) Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes. Diabetologia, 48, 838–848.
Citing Literature
