Wheat gluten protein and the physiology of the ghrelin hormone in chickens: a novel therapeutic approach
Article Sidebar
Main Article Content
This work is licensed under a Creative Commons Attribution 4.0 International License.
-
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Abstract
Ghrelin, a 26-amino acid peptide, is known to stimulate the release of growth hormone and motilin in chickens. Wheat is a staple food in many countries, and the whole grain contains 13% protein, 75% of which is gluten protein. Wheat gluten is hydrolyzed by digestive enzymes, producing gliadin and gluten-exorphin. Gluten-exorphin acts on the gastrointestinal mu receptor and can slow down motility, providing an anti-diarrheal effect. Wheat gluten has also been found to have hepatoprotective effects in rats. Recent studies suggest that gluten may also have ghrelin-like effects in rats, which could promote growth and provide other health benefits. This review article focuses on the potential pharmaceutical applications of wheat seed compounds, including the use of whole wheat in poultry feed and the development of pharmaceuticals using in-vitro hydrolyzed gluten protein. This study provides a comprehensive review of the pharmacological and nutritional properties of wheat gluten protein in poultry and other animals, with an emphasis on its potential as a source of anti-diarrheal, hepatoprotective, and growth-promoting agents.
References
Pourazadi Z, Salari S, Tabandeh MR, Abdollahi MR. Effect of particle size of insoluble fibre on growth performance, apparent ileal digestibility and caecal microbial population in broiler chickens fed barley-containing diets. British Poultry Science 2020;61:734-45.
Svihus B, Juvik E, Hetland H, Krogdahl Å. Causes for improvement in nutritive value of broiler chicken diets with whole wheat instead of ground wheat. British Poultry Science 2004;45:55-60.
Amerah A. Interactions between wheat characteristics and feed enzyme supplementation in broiler diets. Animal Feed Science and Technology 2015;199:1-9.
Zhao H, Shen C, Wu Z, Zhang Z, Xu C. Comparison of wheat, soybean, rice, and pea protein properties for effective applications in food products. Journal of food biochemistry 2020;44:e13157.
Goel G, Tye-Din JA, Qiao S-W, Russell AK, Mayassi T, Ciszewski C, et al. Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Science Advances 2019;5:eaaw7756.
Tye-Din JA, Stewart JA, Dromey JA, Beissbarth T, van Heel DA, Tatham A, et al. Comprehensive, Quantitative Mapping of T Cell Epitopes in Gluten in Celiac Disease. Science Translational Medicine 2010;2:41ra51-41ra51.
Frick R, Høydahl LS, Petersen J, du Pré MF, Kumari S, Berntsen G, et al. A high-affinity human TCR-like antibody detects celiac disease gluten peptide-MHC complexes and inhibits T cell activation. Science Immunology 2021;6:eabg4925.
Shan L, Molberg Ø, Parrot I, Hausch F, Filiz F, Gray GM, et al. Structural Basis for Gluten Intolerance in Celiac Sprue. Science 2002;297:2275-9.
Zis P, Hadjivassiliou M. Treatment of neurological manifestations of gluten sensitivity and coeliac disease. Current treatment options in neurology 2019;21:1-10.
Fukudome S-i, Jinsmaa Y, Matsukawa T, Sasaki R, Yoshikawa M. Release of opioid peptides, gluten exorphins by the action of pancreatic elastase. FEBS letters 1997;412:475-9.
Sato K, Egashira Y, Ono S, Mochizuki S, Shimmura Y, Suzuki Y, et al. Identification of a hepatoprotective peptide in wheat gluten hydrolysate against D-galactosamine-induced acute hepatitis in rats. Journal of agricultural and food chemistry 2013;61:6304-10.
Tanikawa K, Kaneko K, Abe S, Nakato J, Tokuyama Y, Odaka S, et al. Wheat‐ ghretropins: novel ghrelin‐ releasing peptides derived from wheat protein. FEBS open bio 2021;11:1144-52.
Thomas J. Opioid-induced bowel dysfunction. Journal of pain and symptom management
;35:103-13.
Crain SM, Shen K-F. Opioids can evoke direct receptor-mediated excitatory effects on sensory neurons. Trends in pharmacological sciences 1990;11:77-81.
Scanes CG, Pierzchala-Koziec K. Perspectives on Endogenous Opioids in Birds. Frontiers in physiology 2018;9:1842.
Haq U, Raies M. Gluten Exorphins: Springer; 2020, p. 71-88.
Stuknytė M, Maggioni M, Cattaneo S, De Luca P, Fiorilli A, Ferraretto A, et al. Release of wheat gluten exorphins A5 and C5 during in vitro gastrointestinal digestion of breadnd pasta and their absorption through an in vitro model of intestinal epithelium. Food Research International 2015;72:208-14.
Maggioni M, Stuknytė M, De Luca P, Cattaneo S, Fiorilli A, De Noni I, et al. Transport of wheat gluten exorphins A5 and C5 through an in vitro model of intestinal epithelium. Food Research International 2016;88:319-26.
Garg S, Apostolopoulos V, Nurgali K, Mishra VK. Evaluation of in silico approach for prediction of presence of opioid peptides in wheat. Journal of Functional Foods 2018;41:34-40.
Pruimboom L, De Punder K. The opioid effects of gluten exorphins: asymptomatic celiac disease. Journal of Health, Population and Nutrition 2015;33:1-8.
Cuitavi J, Hipólito L, Canals M. The Life Cycle of the Mu-Opioid Receptor. Trends in Biochemical Sciences 2021;46:315-28.
Singh Y, Molan AL, Ravindran V. Influence of the method of whole wheat inclusion on performance and caecal microbiota profile of broiler chickens. Journal of Applied Animal Nutrition 2019;7.
Whiteley P, Shattock P, Knivsberg A-M, Seim A, Reichelt KL, Todd L, et al. Gluten-and casein-free dietary intervention for autism spectrum conditions. Frontiers in human neuroscience 2013;6:344.
Shirako S, Kojima Y, Tomari N, Nakamura Y, Matsumura Y, Ikeda K, et al. Pyroglutamyl leucine, a peptide in fermented foods, attenuates dysbiosis by increasing host antimicrobial peptide. NPJ science of food 2019;3:1-9.
Nepali S, Ki HH, Lee JH, Cha JY, Lee YM, Kim DK. Triticum aestivum sprout-derived polysaccharide exerts hepatoprotective effects against ethanol-induced liver damage by enhancing the antioxidant system in mice. Int J Mol Med 2017;40:1243-52.
Ebeid HM, Gibriel AA, Al-Sayed HM, Elbehairy SA, Motawe EH. Hepatoprotective and antioxidant effects of wheat, carrot, and mango as nutraceutical agents against CCl4- induced hepatocellular toxicity. J Am Coll Nutr 2015;34:228-31.
Lim JY, Yun DH, Lee JH, Kwon YB, Lee YM, Lee DH, et al. Extract of Triticum aestivum Sprouts Suppresses Acetaminophen-Induced Hepatotoxicity in Mice by Inhibiting Oxidative Stress. Molecules 2021;26.
Oishi M, Kiyono T, Sato K, Tokuhara K, Tanaka Y, Miki H, et al. pyroGlu-Leu inhibits the induction of inducible nitric oxide synthase in interleukin-1β-stimulated primary cultured rat hepatocytes. Nitric Oxide 2015;44:81-7.
Kaibori M, Okumura T, Sato K, Nishizawa M, Kon M. Inducible Nitric Oxide Synthase Expression in Liver Injury: Liver Protective Effects on Primary Rat Hepatocytes. Inflamm Allergy Drug Targets 2015;14:77-83.
Sakata I, Sakai T. Ghrelin cells in the gastrointestinal tract. International journal of peptides 2010;2010.
Kaiya H, Van Der Geyten S, Kojima M, Hosoda H, Kitajima Y, Matsumoto M, et al. Chicken ghrelin: purification, cDNA cloning, and biological activity. Endocrinology 2002;143:3454-63.
Richards MP, Poch SM, McMurtry JP. Characterization of turkey and chicken ghrelin genes, and regulation of ghrelin and ghrelin receptor mRNA levels in broiler chickens. General and Comparative Endocrinology 2006;145:298-310.
Weickert MO, Spranger J, Holst JJ, Otto B, Koebnick C, Möhlig M, et al. Wheat-fibre- induced changes of postprandial peptide YY and ghrelin responses are not associated with acute alterations of satiety. Br J Nutr 2006;96:795-8.
Costabile G, Griffo E, Cipriano P, Vetrani C, Vitale M, Mamone G, et al. Subjective satiety and plasma PYY concentration after wholemeal pasta. Appetite 2018;125:172-81.
Russo F, Chimienti G, Clemente C, Ferreri C, Orlando A, Riezzo G. A possible role for ghrelin, leptin, brain-derived neurotrophic factor and docosahexaenoic acid in reducing the quality of life of coeliac disease patients following a gluten-free diet. European journal of nutrition 2017;56:807-18.
Kaneko K. Appetite regulation by plant-derived bioactive peptides for promoting health. Peptides 2021;144:170608.
Richards MP, McMurtry JP. The avian proghrelin system. International journal of peptides 2010;2010.
Ikenoya C, Takemi S, Kaminoda A, Aizawa S, Ojima S, Gong Z, et al. β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification. Scientific Reports 2018;8:9176.
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth- hormone-releasing acylated peptide from stomach. Nature 1999;402:656-60.
Dickson SL. Ghrelin’s effects on growth hormone release: to pulse or not to pulse? Nature Reviews Endocrinology 2022;18:457-.
Kaiya H, Furuse M, Miyazato M, Kangawa K. Current knowledge of the roles of ghrelin in regulating food intake and energy balance in birds. General and comparative endocrinology 2009;163:33-8.
Kaiya H, Miyazato M, Kangawa K, Peter RE, Unniappan S. Ghrelin: a multifunctional hormone in non-mammalian vertebrates. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 2008;149:109-28.
Kaiya H, Darras VM, Kangawa K. Ghrelin in birds: its structure, distribution and function. The Journal of Poultry Science 2007;44:1-18.
Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone. Cell 2008;132:387-96.
Abizaid A, Hougland JL. Ghrelin Signaling: GOAT and GHS-R1a Take a LEAP in Complexity. Trends in Endocrinology & Metabolism 2020;31:107-17.
Liu H, Sun D, Myasnikov A, Damian M, Baneres J-L, Sun J, et al. Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren. Nature Communications 2021;12:6410.
Clemmensen C, Müller TD, Woods SC, Berthoud H-R, Seeley RJ, Tschöp MH. Gut- Brain Cross-Talk in Metabolic Control. Cell 2017;168:758-74.
Li J, Zhong L, Wang F, Zhu H. Dissecting the role of AMP-activated protein kinase in human diseases. Acta Pharmaceutica Sinica B 2017;7:249-59.
Broglio F, Papotti M, Muccioli G, Ghigo E. Brain-gut communication: cortistatin, somatostatin and ghrelin. Trends in Endocrinology & Metabolism 2007;18:246-51.
Sundaram V, Fang JC. Gastrointestinal and Liver Issues in Heart Failure. Circulation 2016;133:1696-703.
Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, et al. Ghrelin strongly stimulates growth hormone release in humans. The journal of clinical endocrinology & metabolism 2000;85:4908-11.
Zhang JV, Ren P-G, Avsian-Kretchmer O, Luo C-W, Rauch R, Klein C, et al. Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake. Science 2005;310:996-9.
Yousufzai MIuA, Harmatz ES, Shah M, Malik MO, Goosens KA. Ghrelin is a persistent biomarker for chronic stress exposure in adolescent rats and humans. Translational Psychiatry 2018;8:74.
Christ A, Lauterbach M, Latz E. Western Diet and the Immune System: An Inflammatory Connection. Immunity 2019;51:794-811.
Gribble FM, Reimann F. Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nature Reviews Endocrinology 2019;15:226-37.
Naufel MF, Pedroso AP, Oyama LM, Telles MM, Hachul H, Ribeiro EB. Preliminary evidence of acylated ghrelin association with depression severity in postmenopausal women. Scientific Reports 2021;11:5319.
Zhang W, Waise TMZ, Toshinai K, Tsuchimochi W, Naznin F, Islam MN, et al. Functional interaction between Ghrelin and GLP-1 regulates feeding through the vagal afferent system. Scientific Reports 2020;10:18415.
Kojima M, Hosoda H, Matsuo H, Kangawa K. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends in Endocrinology & Metabolism 2001;12:118-22.
Rouault AAJ, Rosselli-Murai LK, Hernandez CC, Gimenez LE, Tall GG, Sebag JA. The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a. Science Signaling 2020;13:4569.
Grahame Hardie D. Regulation of AMP-activated protein kinase by natural and synthetic activators. Acta Pharmaceutica Sinica B 2016;6:1-19.
Yang Y, Atasoy D, Su HH, Sternson SM. Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell 2011;146:992-1003.
Chen Y-C, Chiang C-F, Chen L-F, Liang P-C, Hsieh W-Y, Lin W-L. Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell- targeting delivery system. Biomaterials 2014;35:4066-81.
Wierup N, Bjorkqvist M, Westrom B, Pierzynowski S, Sundler F, Sjölund K. Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine. The Journal of Clinical Endocrinology & Metabolism 2007;92:3573-81.
Coll AP, Farooqi IS, O'Rahilly S. The Hormonal Control of Food Intake. Cell
;129:251-62.
van der Klaauw Agatha A, Farooqi IS. The Hunger Genes: Pathways to Obesity. Cell
;161:119-32.
Date Y, Shimbara T, Koda S, Toshinai K, Ida T, Murakami N, et al. Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus. Cell Metabolism 2006;4:323-31.
Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature 2001;409:194-8.
Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346:1623-30.
Shousha S, Nakahara K, Kojima M, Miyazato M, Hosoda H, Kangawa K, et al. Different effects of peripheral and central ghrelin on regulation of food intake in the Japanese quail. General and comparative endocrinology 2005;141:178-83.
Saito E-S, Kaiya H, Tachibana T, Tomonaga S, Denbow DM, Kangawa K, et al. Inhibitory effect of ghrelin on food intake is mediated by the corticotropin-releasing factor system in neonatal chicks. Regulatory peptides 2005;125:201-8.
Chebani Y, Marion C, Zizzari P, Chettab K, Pastor M, Korostelev M, et al. Enhanced responsiveness of Ghsr Q343X rats to ghrelin results in enhanced adiposity without increased appetite. Science Signaling 2016;9:ra39-ra.
Ceron-Romero N, Taofeek N, Thomas A, Vroonland E, Sanmartin K, Verghese M, et al. Capromorelin, a Ghrelin Receptor Agonist, Increases Feed Intake and Body Weight Gain in Broiler Chickens (Gallus gallus domesticus). Poultry Science 2021:101204.
Chinen K, Sakata N, Yoshimatsu G, Nakamura M, Kodama S. Therapeutic effects of acylated ghrelin-specific receptor GHS-R1a antagonist in islet transplantation. Scientific Reports 2021;11:21239.
Davis EA, Wald HS, Suarez AN, Zubcevic J, Liu CM, Cortella AM, et al. Ghrelin Signaling Affects Feeding Behavior, Metabolism, and Memory through the Vagus Nerve. Current Biology 2020;30:4510-8.e6.
Ge X, Wang Y, Lam KSL, Xu A. Metabolic actions of FGF21: molecular mechanisms and therapeutic implications. Acta Pharmaceutica Sinica B 2012;2:350-7.
Yanagi S, Sato T, Kangawa K, Nakazato M. The Homeostatic Force of Ghrelin. Cell Metabolism 2018;27:786-804.
Auclair N, Patey N, Melbouci L, Ou Y, Magri-Tomaz L, Sané A, et al. Acylated Ghrelin and The Regulation of Lipid Metabolism in The Intestine. Scientific Reports 2019;9:17975.
Green CB, Takahashi JS, Bass J. The Meter of Metabolism. Cell 2008;134:728-42.
Pradhan G, Samson SL, Sun Y. Ghrelin: much more than a hunger hormone. Curr Opin Clin Nutr Metab Care 2013;16:619-24.
DiGruccio MR, Mawla AM, Donaldson CJ, Noguchi GM, Vaughan J, Cowing-Zitron C, et al. Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets. Molecular metabolism 2016;5:449-58.
Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. The Lancet 2017;389:2239-51.
Davis J. Hunger, ghrelin and the gut. Brain Res 2018;1693:154-8.
Gimeno RE, Briere DA, Seeley RJ. Leveraging the Gut to Treat Metabolic Disease. Cell Metabolism 2020;31:679-98.
Cao J-M, Ong H, Chen C. Effects of ghrelin and synthetic GH secretagogues on the cardiovascular system. Trends in Endocrinology & Metabolism 2006;17:13-8.
Nonaka M, Kurebayashi N, Murayama T, Sugihara M, Hosoda H, Kishida S, et al. Therapeutic Effects of Ghrelin and Des-Acyl Ghrelin on Doxorubicin-Induced Cardiotoxicity. Biophysical Journal 2018;114:140a.
Zhan D, Du C, Morimoto S, Akiyama T, Schwenke DO, Hosoda H, et al. The Treatment Benefit of Ghrelin on a Mouse Model of Inherited Dilated Cardiomyopathy Caused by Troponin Mutation. Biophysical Journal 2015;108:596a.
Tokudome T, Otani K, Miyazato M, Kangawa K. Ghrelin and the heart. Peptides
;111:42-6.
Ezquerro S, Frühbeck G, Rodríguez A. Ghrelin and autophagy. Curr Opin Clin Nutr Metab Care 2017;20:402-8.
Galluzzi L, Pietrocola F, Levine B, Kroemer G. Metabolic Control of Autophagy. Cell
;159:1263-76.
Zhang H, Li Q, Teng Y, Lin Y, Li S, Qin T, et al. Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3—mechanistic target of rapamycin signaling. Acta Pharmaceutica Sinica B 2020;10:837-49.
Ferrell JM, Chiang JYL. Circadian rhythms in liver metabolism and disease. Acta Pharmaceutica Sinica B 2015;5:113-22.
Mani BK, Zigman JM. Ghrelin as a Survival Hormone. Trends in Endocrinology & Metabolism 2017;28:843-54.
Jing X, Ren D, Gao F, Chen Y, Wu X, Han Y, et al. Gene deficiency or pharmacological inhibition of PDCD4-mediated FGR signaling protects against acute kidney injury. Acta Pharmaceutica Sinica B 2021;11:394-405.
Levey AS, Coresh J. Chronic kidney disease. The Lancet 2012;379:165-80.
Lin L, Chi J, Yan Y, Luo R, Feng X, Zheng Y, et al. Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era. Acta Pharmaceutica Sinica B 2021;11:2609-44.