Ghrelin, food intake, and botanical extracts: A Review

Document Type: Review Article

Authors

1 Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Institute of Genetics and Developmental Biology, International College, University of Chinese Academy of Science (IC-UCAS), Beijing, China

Abstract

A kind of growth hormone secretagogue (GHS), ghrelin, was first isolated from the rat stomach and plays a major role in the activation of the growth hormone secretagogue receptor 1a (GHS-R1a) resulting the release of growth hormone (GH). The preproghrelin gene is placed on chromosome 3, at locus 3p25 –2 in humans and constitutes five exons and three introns. Ghrelin is most plentifully expressed in particular cells in the oxyntic glands of the gastric epithelium, initially named X/A-like cells. Almost 60-70% of circulating ghrelin is secreted by the stomach. Plasma ghrelin concentration alters throughout the day. Ghrelin has been suggested to act as a meal initiator because of its appetite-stimulating influences in free feeding rats in short period. In addition to ghrelin’s function as a meal motivator, it seems to contribute in long-term energy balance and nutritional status. In addition, many studies have been carried out in order to investigate the effects of natural and medicinal plants and botanical extracts on appetite, food intake, energy hemostasis, and the level of related hormones including ghrelin. Due to the importance of ghrelin in nutritional and medical sciences, this review was performed to understand new aspects of this hormone’s function.

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Abu-Farha M ,Dehbi M. 2014. Gender differences in ghrelin association with cardiometabolic risk factors in arab population. 2014: 730472.

Arafat M A, Otto B, Rochlitz H, Tschop M, Bahr V, Mohlig M, Diederich S, Spranger J ,Pfeiffer A F. 2005. Glucagon inhibits ghrelin secretion in humans. Eur J Endocrinol, 153: 397-402.

Avula B, Wang Y H, Pawar R S, Shukla Y J, Schaneberg B ,Khan I A. 2006. Determination of the appetite suppressant P57 in Hoodia gordonii plant extracts and dietary supplements by liquid chromatography/electrospray ionization mass spectrometry (LC-MSD-TOF) and LC-UV methods. J AOAC Int, 89: 606-11.

Barkan A L, Dimaraki E V, Jessup S K, Symons K V, Ermolenko M ,Jaffe C A. 2003. Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. J Clin Endocrinol Metab, 88: 2180-4.

Barreiro M L, Gaytan F, Caminos J E, Pinilla L, Casanueva F F, Aguilar E, Dieguez C ,Tena-Sempere M. 2002. Cellular location and hormonal regulation of ghrelin expression in rat testis. Biol Reprod, 67: 1768-76.

Bednarek M A, Feighner S D, Pong S S, Mckee K K, Hreniuk D L, Silva M V, Warren V A, Howard A D, Van Der Ploeg L H ,Heck J V. 2000. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem, 43: 4370-6.

Cao Y, Tang J, Yang T, Ma H, Yi D, Gu C ,Yu S. 2013. Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response. PLoS One, 8: e55021.

Chan J L, Bullen J, Lee J H, Yiannakouris N ,Mantzoros C S. 2004. Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects. J Clin Endocrinol Metab, 89: 335-43.

Choi K, Roh S G, Hong Y H, Shrestha Y B, Hishikawa D, Chen C, Kojima M, Kangawa K ,Sasaki S. 2003. The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis. Endocrinology, 144: 754-9.

Coll A P, Farooqi I S ,O'rahilly S. 2007. The hormonal control of food intake. Cell, 129: 251-62.

Cowley M A, Smith R G, Diano S, Tschop M, Pronchuk N, Grove K L, Strasburger C J, Bidlingmaier M, Esterman M, Heiman M L, Garcia-Segura L M, Nillni E A, Mendez P, Low M J, Sotonyi P, Friedman J M, Liu H, Pinto S, Colmers W F, Cone R D ,Horvath T L. 2003. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron, 37: 649-61.

Cummings D E, Purnell J Q, Frayo R S, Schmidova K, Wisse B E ,Weigle D S. 2001. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes, 50: 1714-9.

Cummings D E, Weigle D S, Frayo R S, Breen P A, Ma M K, Dellinger E P ,Purnell J Q. 2002. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med, 346: 1623-30.

Cupp M J 2000. Toxicology and clinical pharmacology of herbal products, Totowa, New Jersey (USA), Humana Press.

Dardzinska J A, Malgorzewicz S, Kaska L, Proczko M, Stefaniak T, Stankiewicz M ,Sledzinski Z. 2014. Fasting and postprandial acyl and desacyl ghrelin levels in obese and non-obese subjects. Endokrynol Pol, 65: 377-81.

Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal M S, Suganuma T, Matsukura S, Kangawa K ,Nakazato M. 2000. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology, 141: 4255-61.

Davis M E, Pemberton C J, Yandle T G, Lainchbury J G, Rademaker M T, Nicholls M G, Frampton C M ,Richards A M. 2004. Urocortin-1 infusion in normal humans. J Clin Endocrinol Metab, 89: 1402-9.

Drazen D L, Vahl T P, D'alessio D A, Seeley R J ,Woods S C. 2006. Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. Endocrinology, 147: 23-30.

Druce M R, Wren A M, Park A J, Milton J E, Patterson M, Frost G, Ghatei M A, Small C ,Bloom S R. 2005. Ghrelin increases food intake in obese as well as lean subjects. Int J Obes (Lond), 29: 1130-6.

Emamghoreishi M, Khasaki M ,Aazam M F. 2005. Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze. J Ethnopharmacol, 96: 365-70.

Emanuel A J ,Ritter S. 2010. Hindbrain catecholamine neurons modulate the growth hormone but not the feeding response to ghrelin. Endocrinology, 151: 3237-46.

English P J, Ghatei M A, Malik I A, Bloom S R ,Wilding J P. 2002. Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab, 87: 2984.

Fleming R M. 2007. The effect of ephedra and high fat dieting: a cause for concern! A case report. Angiology, 58: 102-5.

Fride E, Bregman T ,Kirkham T C. 2005. Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Exp Biol Med (Maywood), 230: 225-34.

Fukushima N, Hanada R, Teranishi H, Fukue Y, Tachibana T, Ishikawa H, Takeda S, Takeuchi Y, Fukumoto S, Kangawa K, Nagata K ,Kojima M. 2005. Ghrelin directly regulates bone formation. J Bone Miner Res, 20: 790-8.

Garcia A L, Otto B, Reich S C, Weickert M O, Steiniger J, Machowetz A, Rudovich N N, Mohlig M, Katz N, Speth M, Meuser F, Doerfer J, Zunft H J, Pfeiffer A H ,Koebnick C. 2007. Arabinoxylan consumption decreases postprandial serum glucose, serum insulin and plasma total ghrelin response in subjects with impaired glucose tolerance. Eur J Clin Nutr, 61: 334-41.

Gazdek D. 2014. [Marijuana for medical purposes--public health perspective]. Lijec Vjesn, 136: 192-9.

Gualillo O, Caminos J, Blanco M, Garcia-Caballero T, Kojima M, Kangawa K, Dieguez C ,Casanueva F. 2001. Ghrelin, a novel placental-derived hormone. Endocrinology, 142: 788-94.

Hansen T K, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen J S ,Jorgensen J O. 2002. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf), 56: 203-6.

Hill B R, Rolls B J, Roe L S, De Souza M J ,Williams N I. 2013. Ghrelin and peptide YY increase with weight loss during a 12-month intervention to reduce dietary energy density in obese women. Peptides, 49: 138-44.

Hosoda H, Kojima M, Matsuo H ,Kangawa K. 2000. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun, 279: 909-13.

Howe S M, Hand T M ,Manore M M. 2014. Exercise-Trained Men and Women: Role of Exercise and Diet on Appetite and Energy Intake. Nutrients, 6: 4935-4960.

Hu M L, Rayner C K, Wu K L, Chuah S K, Tai W C, Chou Y P, Chiu Y C, Chiu K W ,Hu T H. 2011. Effect of ginger on gastric motility and symptoms of functional dyspepsia. World J Gastroenterol, 17: 105-10.

Isaksson H, Fredriksson H, Andersson R, Olsson J ,Aman P. 2009. Effect of rye bread breakfasts on subjective hunger and satiety: a randomized controlled trial. Nutr J, 8: 39.

Isgaard J ,Granata R. 2011. Ghrelin in cardiovascular disease and atherogenesis. Mol Cell Endocrinol, 340: 59-64.

Isomoto H, Ueno H, Saenko V A, Mondal M S, Nishi Y, Kawano N, Ohnita K, Mizuta Y, Ohtsuru A, Yamashita S, Nakazato M ,Kohno S. 2005. Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans. Am J Gastroenterol, 100: 1711-20.

Khatib N, Gaidhane S, Gaidhane A M, Khatib M, Simkhada P, Gode D ,Zahiruddin Q S. 2014. Ghrelin: ghrelin as a regulatory Peptide in growth hormone secretion. J Clin Diagn Res, 8: Mc13-7.

Kim Y S, Lee J S, Lee T H, Cho J Y, Kim J O, Kim W J, Kim H G, Jeon S R ,Jeong H S. 2012. Plasma levels of acylated ghrelin in patients with functional dyspepsia. World J Gastroenterol, 18: 2231-7.

Kirkham T C. 2005. Endocannabinoids in the regulation of appetite and body weight. Behav Pharmacol, 16: 297-313.

Kirkham T C ,Williams C M. 2001. Endogenous cannabinoids and appetite. Nutr Res Rev, 14: 65-86.

Klok M D, Jakobsdottir S ,Drent M L. 2007. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev, 8: 21-34.

Klontz K C, Timbo B B ,Street D. 2006. Consumption of dietary supplements containing Citrus aurantium (bitter orange)--2004 California Behavioral Risk Factor Surveillance Survey (BRFSS). Ann Pharmacother, 40: 1747-51.

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H ,Kangawa K. 1999. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402: 656-60.

Kojima M, Hosoda H ,Kangawa K. 2004. Clinical endocrinology and metabolism. Ghrelin, a novel growth-hormone-releasing and appetite-stimulating peptide from stomach. Best Pract Res Clin Endocrinol Metab, 18: 517-30.

Kojima M, Hosoda H, Matsuo H ,Kangawa K. 2001. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab, 12: 118-22.

Kojima M ,Kangawa K. 2005. Ghrelin: structure and function. Physiol Rev, 85: 495-522.

Koleva D I, Orbetzova M M ,Atanassova P K. 2013. Adipose tissue hormones and appetite and body weight regulators in insulin resistance. Folia Med (Plovdiv), 55: 25-32.

Kuriyan R, Raj T, Srinivas S K, Vaz M, Rajendran R ,Kurpad A V. 2007. Effect of Caralluma fimbriata extract on appetite, food intake and anthropometry in adult Indian men and women. Appetite, 48: 338-44.

Laviano A, Molfino A, Rianda S ,Rossi Fanelli F. 2012. The growth hormone secretagogue receptor (Ghs-R). Curr Pharm Des, 18: 4749-54.

Le Roux C W, Patterson M, Vincent R P, Hunt C, Ghatei M A ,Bloom S R. 2005. Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects. J Clin Endocrinol Metab, 90: 1068-71.

Lu S, Guan J L, Wang Q P, Uehara K, Yamada S, Goto N, Date Y, Nakazato M, Kojima M, Kangawa K ,Shioda S. 2002. Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci Lett, 321: 157-60.

Luiking Y C, Akkermans L M, Van Der Reijden A C, Peeters T L ,Van Berge-Henegouwen G P. 2003. Differential effects of motilin on interdigestive motility of the human gastric antrum, pylorus, small intestine and gallbladder. Neurogastroenterol Motil, 15: 103-11.

Macke C, Prenzler N K, Horn R, Brabant G ,Nave H. 2009. Ghrelin treatment increases receptor-bound leptin in healthy and endotoxemic obese Lewis rats. Exp Clin Endocrinol Diabetes, 117: 473-9.

Mansour M S, Ni Y M, Roberts A L, Kelleman M, Roychoudhury A ,St-Onge M P. 2012. Ginger consumption enhances the thermic effect of food and promotes feelings of satiety without affecting metabolic and hormonal parameters in overweight men: a pilot study. Metabolism, 61: 1347-52.

Martin J R, Lieber S B, Mcgrath J, Shanabrough M, Horvath T L ,Taylor H S. 2011. Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming. Endocrinology, 152: 2060-6.

Matsumura K, Tsuchihashi T, Fujii K, Abe I ,Iida M. 2002. Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension, 40: 694-9.

Mazidi M, Baghban Taraghdari S, Rezaee P, Kamgar M, Jomezadeh M R, Akbarieh Hasani O, Soukhtanloo M, Hosseini M, Gholamnezhad Z, Rakhshandeh H, Norouzy A, Esmaily H, Patterson M ,Nematy M. 2014a. The effect of hydroalcoholic extract of Cannabis Sativa on appetite hormone in rat. J Complement Integr Med, 11: 253-7.

Mazidi M, Nematy M, Taraghdari S B, Soukhtanloo M, Hosseini M, Rakhshandeh H, Norouzy A ,Esmaily H. 2014b. Hydroalcoholic extract of Coriandrum sativum had no effect on ghrelin hormone in rat. Journal of Medicinal Plants Studies. Journal of Medicinal Plants Studies, 2: 147-150.

Miki K, Maekura R, Nagaya N, Nakazato M, Kimura H, Murakami S, Ohnishi S, Hiraga T, Miki M, Kitada S, Yoshimura K, Tateishi Y, Arimura Y, Matsumoto N, Yoshikawa M, Yamahara K ,Kangawa K. 2012. Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial. PLoS One, 7: e35708.

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. J Clin Endocrinol Metab, 88: 5510-4.

Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K ,Matsukura S. 2001. A role for ghrelin in the central regulation of feeding. Nature, 409: 194-8.

Narimani-Rad M, Lotfi A, Abbasi M M ,Abdollahi B. 2013. The Effect of Cornelian Cherry (Cornus mas L.) Extract on Serum Ghrelin and Corticosterone Levels in Rat Model. J. Pharm. Biomed. Sci, 3: 7-9.

Neary N M, Small C J, Wren A M, Lee J L, Druce M R, Palmieri C, Frost G S, Ghatei M A, Coombes R C ,Bloom S R. 2004. Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab, 89: 2832-6.

Nematy M, Brynes A E, Hornick P I, Patterson M, Ghatei M A, Bloom S R, Brett S J ,Frost G S. 2007. Postprandial ghrelin suppression is exaggerated following major surgery; implications for nutritional recovery. Nutr Metab (Lond), 4: 20.

Nematy M, Kamgar M, Mohajeri S M, Tabatabaei Zadeh S A, Jomezadeh M R, Akbarieh Hasani O, Kamali N, Vojouhi S, Baghban S, Aghaei A, Soukhtanloo M, Hosseini M, Gholamnezhad Z, Rakhshandeh H, Norouzy A, Esmaily H, Ghayour-Mobarhan M ,Patterson M. 2013. The effect of hydroalcoholic extract of Coriandrum sativum on rat appetite. Avicenna J Phytomed, 3: 91-7.

Nematy M, O'flynn J E, Wandrag L, Brynes A E, Brett S J, Patterson M, Ghatei M A, Bloom S R ,Frost G S. 2006. Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study. Crit Care, 10: R10.

Norrelund H, Hansen T K, Orskov H, Hosoda H, Kojima M, Kangawa K, Weeke J, Moller N, Christiansen J S ,Jorgensen J O. 2002. Ghrelin immunoreactivity in human plasma is suppressed by somatostatin. Clin Endocrinol (Oxf), 57: 539-46.

Ohia S E, Opere C A, Leday A M, Bagchi M, Bagchi D ,Stohs S J. 2002. Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Mol Cell Biochem, 238: 89-103.

Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl R L, Heiman M L, Lehnert P, Fichter M ,Tschop M. 2001. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol, 145: 669-73.

Otto B, Tschop M ,Cuntz U. 2004a. Letter to the Editor: Similar fasting ghrelin levels in binge eating/purging anorexia nervosa and restrictive anorexia nervosa. Psychoneuroendocrinology, 29: 692-3.

Otto B, Tschop M, Fruhauf E, Heldwein W, Fichter M, Otto C ,Cuntz U. 2005. Postprandial ghrelin release in anorectic patients before and after weight gain. Psychoneuroendocrinology, 30: 577-81.

Otto B, Tschop M, Heldwein W, Pfeiffer A F ,Diederich S. 2004b. Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans. Eur J Endocrinol, 151: 113-7.

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: 845-50.

Perry B ,Wang Y. 2012. Appetite regulation and weight control: the role of gut hormones. Nutr Diabetes, 2: e26.

Prado C L, Pugh-Bernard A E, Elghazi L, Sosa-Pineda B ,Sussel L. 2004. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci U S A, 101: 2924-9.

Qi X, Reed J, Englander E W, Chandrashekar V, Bartke A ,Greeley G H, Jr. 2003. Evidence that growth hormone exerts a feedback effect on stomach ghrelin production and secretion. Exp Biol Med (Maywood), 228: 1028-32.

Rayalam S, Della-Fera M A ,Baile C A. 2008. Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem, 19: 717-26.

Riggs P K, Vaida F, Rossi S S, Sorkin L S, Gouaux B, Grant I ,Ellis R J. 2012. A pilot study of the effects of cannabis on appetite hormones in HIV-infected adult men. Brain Res, 1431: 46-52.

Riis A L, Hansen T K, Moller N, Weeke J ,Jorgensen J O. 2003. Hyperthyroidism is associated with suppressed circulating ghrelin levels. J Clin Endocrinol Metab, 88: 853-7.

Robertson M D, Henderson R A, Vist G E ,Rumsey R D. 2004. Plasma ghrelin response following a period of acute overfeeding in normal weight men. Int J Obes Relat Metab Disord, 28: 727-33.

Rojdmark S, Calissendorff J, Danielsson O ,Brismar K. 2005. Hunger-satiety signals in patients with Graves' thyrotoxicosis before, during, and after long-term pharmacological treatment. Endocrine, 27: 55-61.

Ruchlemer R, Amit-Kohn M, Raveh D ,Hanus L. 2014. Inhaled medicinal cannabis and the immunocompromised patient. Support Care Cancer.

Sansone R A ,Sansone L A. 2014. The interface: marijuana and body weight. Innov Clin Neurosci, 11: 50-4.

Scerif M, Goldstone A P ,Korbonits M. 2011. Ghrelin in obesity and endocrine diseases. Mol Cell Endocrinol, 340: 15-25.

Seim I, Collet C, Herington A C ,Chopin L K. 2007. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics, 8: 298.

Sengupta K, Mishra A T, Rao M K, Sarma K V, Krishnaraju A V ,Trimurtulu G. 2012. Efficacy of an herbal formulation LI10903F containing Dolichos biflorus and Piper betle extracts on weight management. Lipids Health Dis, 11: 176.

Shen J, Niijima A, Tanida M, Horii Y, Maeda K ,Nagai K. 2005. Olfactory stimulation with scent of lavender oil affects autonomic nerves, lipolysis and appetite in rats. Neurosci Lett, 383: 188-93.

Tack J, Depoortere I, Bisschops R, Delporte C, Coulie B, Meulemans A, Janssens J ,Peeters T. 2006. Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut, 55: 327-33.

Takachi K, Doki Y, Ishikawa O, Miyashiro I, Sasaki Y, Ohigashi H, Murata K, Nakajima H, Hosoda H, Kangawa K, Sasakuma F ,Imaoka S. 2006. Postoperative ghrelin levels and delayed recovery from body weight loss after distal or total gastrectomy. J Surg Res, 130: 1-7.

Tena-Sempere M, Barreiro M L, Gonzalez L C, Gaytan F, Zhang F P, Caminos J E, Pinilla L, Casanueva F F, Dieguez C ,Aguilar E. 2002. Novel expression and functional role of ghrelin in rat testis. Endocrinology, 143: 717-25.

Thompson N M, Gill D A, Davies R, Loveridge N, Houston P A, Robinson I C ,Wells T. 2004. Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology, 145: 234-42.

Tritos N A, Kokkinos A, Lampadariou E, Alexiou E, Katsilambros N ,Maratos-Flier E. 2003. Cerebrospinal fluid ghrelin is negatively associated with body mass index. J Clin Endocrinol Metab, 88: 2943-6.

Tritos N A ,Kokkotou E G. 2006. The physiology and potential clinical applications of ghrelin, a novel peptide hormone. Mayo Clin Proc, 81: 653-60.

Tschop M, Smiley D L ,Heiman M L. 2000. Ghrelin induces adiposity in rodents. Nature, 407: 908-13.

Tschop M, Wawarta R, Riepl R L, Friedrich S, Bidlingmaier M, Landgraf R ,Folwaczny C. 2001. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest, 24: Rc19-21.

Ueki S, Miyoshi M, Shido O, Hasegawa J ,Watanabe T. 2008. Systemic administration of [6]-gingerol, a pungent constituent of ginger, induces hypothermia in rats via an inhibitory effect on metabolic rate. Eur J Pharmacol, 584: 87-92.

Ukkola O. 2011. Ghrelin in Type 2 diabetes mellitus and metabolic syndrome. Mol Cell Endocrinol, 340: 26-8.

Usta J, Kreydiyyeh S, Knio K, Barnabe P, Bou-Moughlabay Y ,Dagher S. 2009. Linalool decreases HepG2 viability by inhibiting mitochondrial complexes I and II, increasing reactive oxygen species and decreasing ATP and GSH levels. Chem Biol Interact, 180: 39-46.

Van Der Lely A J, Tschop M, Heiman M L ,Ghigo E. 2004. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev, 25: 426-57.

Vinkx C J A ,Delcour J A. 1996. Rye (Secale cerealeL.) Arabinoxylans: A Critical Review. Journal of Cereal Science, 24: 1-14.

Vivenza D, Rapa A, Castellino N, Bellone S, Petri A, Vacca G, Aimaretti G, Broglio F ,Bona G. 2004. Ghrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric data in children and adolescents. Eur J Endocrinol, 151: 127-33.

Waissengrin B, Urban D, Leshem Y, Garty M ,Wolf I. 2014. Patterns of Use of Medical Cannabis Among Israeli Cancer Patients: A Single Institution Experience. J Pain Symptom Manage.

Walker A K, Gong Z, Park W M, Zigman J M ,Sakata I. 2013. Expression of Serum Retinol Binding Protein and Transthyretin within Mouse Gastric Ghrelin Cells. PLoS One, 8: e64882.

Weigle D S, Cummings D E, Newby P D, Breen P A, Frayo R S, Matthys C 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. J Clin Endocrinol Metab, 88: 1577-86.

Wierup N, Yang S, Mcevilly R J, Mulder H ,Sundler F. 2004. Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. J Histochem Cytochem, 52: 301-10.

Wren A M ,Bloom S R. 2007. Gut hormones and appetite control. Gastroenterology, 132: 2116-30.

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. J Clin Endocrinol Metab, 86: 5992.