Differential Effects of High-fat and High-carbohydrate Content Isoenergetic Meals on Plasma Active Ghrelin Concentrations in Lean and Obese Women

Abstract

Aim: To study the effect of two different isoenergetic meals, one rich in carbohydrates and one rich in fat, on plasma active ghrelin levels in lean or obese subjects. Methods: Eight obese and eight lean women, strictly matched for age, were fed two isoenergetic meals of different composition, one rich in fat and one rich in carbohydrates (CHO), on separate days. Plasma active ghrelin levels were measured just before and at 1, 2 and 3 hours after meal consumption. Results: Overall, plasma active ghrelin levels were significantly lower in the obese compared to the lean women (71.7 ± 29.7 vs. 222.2 ± 127.2 pmol/liter respectively, p < 0.0001). Furthermore, ghrelin levels decreased significantly by 30 % from baseline values in the lean subjects in the first hour after the CHO-rich meal (mean difference ± SD): - 66.2 ± 49.0 pmol/liter (p = 0.03), returning to near-baseline levels by 2 hours, while no significant change was observed in the obese subjects. After the fat-rich meal, active ghrelin levels did not change significantly in either group (p > 0.05). Conclusions: A fat-rich meal does not suppress plasma active ghrelin levels in either lean or obese women. Moreover, in obese, unlike lean women, a high carbohydrate meal also fails to suppress plasma ghrelin levels, which are already quite low. This suggests that ghrelin-induced satiety mechanisms may be compromised in these subjects.

Neuropeptides - Postprandial - Feeding - Energy expenditure - Obesity

References

• 1 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach.  Nature. 1999;  402 656-660
• 2 Hataya Y, Akamizu T, Takaya K, Kanamoto N, Ariyasu H, Saijo M, Moriyama K, Shimatsu A, Kojima M, Kangawa K, Nakao K. A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GH-releasing hormone in humans.  J Clin Endocrinol Metab. 2001;  86 4552
• 3 Mozid A M, Tringali G, Forsling M L, Hendricks M S, Ajodha S, Edwards R, Navarra P, Grossman A B, Korbonits M. Ghrelin id released from rat hypothalamic explants and stimulates corticotrophin-releasing hormone and arginine-vasopresin.  Horm Metab Res. 2003;  35 455-459
• 4 Peino R, Baldelli R, Rodriguez-Garcia J, Rodriguez-Segade S, Kojima M, Kangawa K, Arvat E, Ghigo E, Dieguez C, Casanueva F F. Ghrelin-induced growth hormone secretion in humans.  Eur J Endocrinol. 2000;  143 R11-R14
• 5 Pinkney J, Williams G. Ghrelin gets hungry.  Lancet. 2002;  359 1360-1361
• 6 Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.  Diabetes. 2001;  50 227-232
• 7 Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S. A role for ghrelin in the central regulation of feeding.  Nature. 2001;  409 194-198
• 8 Cummings D E, Purnell J Q, Frayo R S, Schmidova K, Wisse B E, Weigle D S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans.  Diabetes. 2001;  50 714-1719
• 9 Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal M S, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion.  J Clin Endocrinol Metab. 2002;  87 240-244
• 10 Hansen T K, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen J S, Jorgensen J O. Weight loss increases circulating levels of ghrelin in human obesity.  Clin Endocrinol (Oxf). 2002;  56 203-206
• 11 English P J, Ghatei M A, Malik I A, Bloom S R, Wilding J P. Food fails to suppress ghrelin levels in obese humans.  J Clin Endocrinol Metab. 2002;  87 2984
• 12 Nakagawa E, Nagaya N, Okumura H, Enomoto M, Oya H, Ono F, Hosoda H, Kojima M, Kangawa K. Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose.  Clin Sci (Lond). 2002;  103 325-328
• 13 Flanagan D E, Evans M L, Monsod T P, Rife F, Heptulla R A, Tamborlane W V, Sherwin R S. The influence of insulin on circulating ghrelin.  Am J Psysiol Endocrinol Metab. 2003;  284 E313-316
• 14 Mohlig M, Spranger J, Otto B, Ristow M, Tschop M, Pfeiffer A F. Euglycemic hyperinsulinemia, but not lipid infusion, decreases circulating ghrelin levels in humans.  J Endocrinol Invest. 2002;  25 RC36-38
• 15 Lee H M, Wang G, Englander E W, Kojima M, Greeley G H. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations.  Endocrinology. 2001;  143 185-190
• 16 Tschop M, Smiley D L, Heiman M L. Ghrelin induces adiposity in rodents.  Nature. 2000;  407 908-913
• 17 Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein H H, Tschop M, Klein J. Direct peripheral effects of ghrelin include suppression of adiponectin expression.  Horm Metab Res. 2002;  34 640-645
• 18 Muccioli G, Tschop M, Papotti M, Deghengi R, Heiman M, Ghigo E. Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity.  Eur J Pharmacol. 2002;  440 235-254
• 19 Tentolouris N, Grapsas E, Stambulis E, Katsilambros N, Papageorgiou K. Impact of body mass on autonomic function in persons with type 2 diabetes.  Diabetes Res Clin Pract. 1999;  46 29-33
• 20 Jequier E. Methods of measuring energy expenditure and substrate utilization.  Diabetes Rev. 1996;  4 423-432
• 21 Friedwald W T, Levy R I, Fredrickson D S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.  Clin Chem. 1972;  18 499-502
• 22 Matthews D R, Hosker J P, Rudenski A S, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 23 Tschop M, Wawarta R, Riepl R L, Friedrich S, Bidlingmaier M, Landgraf R, Folwaczny C. Post-prandial decrease of circulating human ghrelin levels.  J Endocrinol Invest. 2001;  24 RC19-21
• 24 Cummings D E, Weigle D S, Frayo R S, Breen P A, Ma M K, Dellinger E P, Purnell J Q. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.  N Engl J Med. 2002;  346 1623-30
• 25 Anderwald C, Brabant G, Bernroider E, Horn R, Brehm A, Waldhausl W, Roden M. Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients.  Diabetes. 2003;  52 1792-1798
• 26 Toshinai K, Mondal M S, Nakazato M, Date Y, Murakami N, Kojima M, Kangawa K, Matsuka S. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration.  Biochem Biophys Res Commun. 2001;  281 1220-1225
• 27 Djurhuus C B, Hansen T K, Gravholt C, Orskov L, Hosoda H, Kangawa K, Jorgensen J O, Holst J J, Schmitz O. Circulating levels of ghrelin and GLP-1 are inversely related during glucose ingestion.  Horm Metab Res. 2002;  34 411-413