Obesity as the Sequel of Childhood Stunting: Ghrelin and GHSR Gene Polymorphism Explained
This review discussed the current status on studies in the nutrigenetic aspects of the relationship between stunting in the childhood and obesity in adulthood. I hypothesized that stunted children are more likely to become obese in their later life because they have lower metabolic rate and higher tendency of fat storage. There are several candidate genes and pathway involved in obesity and I suspected that ghrelin and its receptor growth hormone secretague receptor (GHSR) were responsible.
De Onis M, Blössner M, Borghi E. Prevalence and trends of stunting among pre-school children, 1990–2020. Public Health Nutr. 2012;15(01):142–8.
International Institute for Population Sciences & Macro International. National Family Health Survey (NFHS-3), 2005–06: India: Volume I. Mumbai; 2007.
Indonesian Ministry of Health. Riset Kesehatan Dasar (Basic Health Surveylence) 2013. 2013;
Poirier P, Eckel RH. Obesity and cardiovascular disease. Curr Atheroscler Rep [Internet]. 2002;4(6):448–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16627822
Kar BR, Rao SL, Chandramouli BA. Cognitive development in children with chronic protein energy malnutrition. Behav Brain Funct [Internet]. 2008;4:31. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18652660"&
Popkin BM, Richards MK, Montiero C a. Stunting is associated with overweight in children of four nations that are undergoing the nutrition transition. J Nutr. 1996;126(12):3009–16.
El Taguri A, Besmar F, Abdel Monem A, Betilmal I, Ricour C, Rolland-Cachera MF. Stunting is a major risk factor for overweight: Results from national surveys in 5 Arab countries. East Mediterr Heal J. 2009;15(3):549–62.
Kimani-Murage EW, Kahn K, Pettifor JM, Tollman SM, Dunger DB, Gomez-Olive XF, et al. The prevalence of stunting, overweight and obesity, and metabolic disease risk in rural South African children. BMC Public Health [Internet]. 2010;10:158. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20338024
Pomeroy E, Stock JT, Stanojevic S, Miranda JJ, Cole TJ, Wells JCK. Stunting, adiposity, and the individual-level “dual burden” among urban lowland and rural highland peruvian children. Am J Hum Biol. 2014;26(4):481–90.
Bénéfice E, Garnier D, Simondon KB, Malina RM. Relationship between stunting in infancy and growth and fat distribution during adolescence in Senegalese girls. Eur J Clin Nutr [Internet]. 2001;55(1):50–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11303494
Savanur MS, Ghugre PS. BMI, body fat and waist-to-height ratio of stunted v. non-stunted Indian children: a case-control study. Public Health Nutr [Internet]. 2016;19(8):1389–96. Available from: http://journals.cambridge.org/abstract_S1368980016000215
Sichieri R, Dos Santos Barbosa F, Moura EC. Relationship between short stature and obesity in Brazil: a multilevel analysis. Br J Nutr. 2010;103(10):1534–8.
Bosy-Westphal A, Plachta-Danielzik S, Dörhöfer R-P, Müller MJ. Short stature and obesity: positive association in adults but inverse association in children and adolescents. Br J Nutr. 2009;102:453–61.
Sawaya a L, Grillo LP, Verreschi I, da Silva a C, Roberts SB. Mild stunting is associated with higher susceptibility to the effects of high fat diets: studies in a shantytown population in São Paulo, Brazil. J Nutr [Internet]. 1998;128(2 Suppl):415S – 420S. Available from: http://jn.nutrition.org/content/128/2/415S.abstract
Sawaya AL, Roberts S. Stunting and future risk of obesity: principal physiological mechanisms. Cad saude publica / Minist da Saude, Fund Oswaldo Cruz, Esc Nac Saude Publica. 2003;19 Suppl 1:S21–8.
Hoffman DJ, Sawaya AL, Verreschi I, Tucker KL, Roberts SB. Why are nutritionally stunted children at increased risk of obesity? Studies of metabolic rate and fat oxidation in shantytown children from Sao Paulo, Brazil. Am J Clin Nutr. 2000;72(3):702–7.
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;409:194–8.
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.
Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000;407:908–13.
Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50(4):707–9.
Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, et al. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol. 2001;145(5).
Wortley KE, Del Rincon JP, Murray JD, Garcia K, Iida K, Thorner MO, et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest. 2005;115(12):3573–8.
Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, et al. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest. 2005;115(12):3564–72.
Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci U S A [Internet]. 2004;101(13):4679–84. Available from: http://www.pnas.org/content/101/13/4679.full
Varela L, Vázquez MJ, Cordido F, Nogueiras R, Vidal-Puig A, Diéguez C, et al. Ghrelin and lipid metabolism: Key partners in energy balance. Journal of Molecular Endocrinology. 2011. p. 43–63.
Nogueiras R, López M, Diéguez C. Regulation of lipid metabolism by energy availability: a role for the central nervous system. Obes Rev. 2010;11(13):185–201.
Whatmore AJ, Hall CM, Jones J, Westwood M, Clayton PE. Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol (Oxf). 2003;59(5):649–54.
Camurdan MO, Bideci A, Demirel F, Cinaz P. Serum ghrelin, IGF-I and IGFBP-3 levels in children with normal variant short stature. Endocr J [Internet]. 2006;53(4):479–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16820702
Şen TA, Şimflek DG, Darcan Ş, Çoker M. Ghrelin levels in children with constitutional delay of growth and puberty. JCRPE J Clin Res Pediatr Endocrinol. 2010;2(3):117–21.
Cruz-Domínguez MP, Cortés DHM, Zarate A, Tapia-González M de los Á, Álvarez-Acosta S, Damasio L, et al. Relationship of ghrelin, acid uric and proinflammatory adipocytokines in different degrees of obesity or diabetes. Int J Clin Exp Med. 2014;7(5):1435–41.
Gutierrez JA, Solenberg PJ, Perkins DR, Willency JA, Knierman MD, Jin Z, et al. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci U S A [Internet]. 2008;105(17):6320–5. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2359796 HYPERLINK "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2359796&tool=pmcentrez&rendertype=abstract"&
Sato T, Ida T, Nakamura Y, Shiimura Y, Kangawa K, Kojima M. Physiological roles of ghrelin on obesity. Obesity Research and Clinical Practice. 2014. p. e405–13.
Liu B, Garcia EA, Korbonits M. Genetic studies on the ghrelin, growth hormone secretagogue receptor (GHSR) and ghrelin O-acyl transferase (GOAT) genes. Peptides. 2011. p. 2191–207.
Asakawa A, Inui A, Kaga T, Katsuura G, Fujimiya M, Fujino MA, et al. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut [Internet]. 2003;52(7):947–52. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12801949"&
Inoue H, Kangawa N, Kinouchi A, Sakamoto Y, Kimura C, Horikawa R, et al. Identification and functional analysis of novel human growth hormone secretagogue receptor (GHSR) gene mutations in Japanese subjects with short stature. J Clin Endocrinol Metab [Internet]. 2011;96(2):E373–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21084395
Pugliese-Pires PN, Fortin JP, Arthur T, Latronico AC, Mendonca BB, Villares SMF, et al. Novel inactivating mutations in the GH secretagogue receptor gene in patients with constitutional delay of growth and puberty. Eur J Endocrinol. 2011;165(2):233–41.
Gueorguiev M, Korbonits M. Genetics of the ghrelin system. The Ghrelin System. 2013. p. 25–40.
Riedl S, Hughes I, Harris M, Leong GM, Beilby J, Sly P, et al. GH secretagogue receptor gene polymorphisms are associated with stature throughout childhood. Eur J Endocrinol. 2012;166(6):1079–85.
Gueorguiev M, Lecoeur C, Benzinou M, Mein CA, Meyre D, Vatin V, et al. A genetic study of the ghrelin and growth hormone secretagogue receptor (GHSR) genes and stature. Ann Hum Genet. 2009;73(1):1–9.
Luglio HF, Inggriyani CG, Huriyati E, Julia M SR. Association of SNPs in GHSR rs292216 and rs509035 on dietary intake in Indonesian obese female adolescents. Int J Mol Epidemiol Genet. 2014;5(4):195–9.
Baessler A, Hasinoff MJ, Fischer M, Reinhard W, Sonnenberg GE, Olivier M, et al. Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity. Diabetes. 2005;54:259–67.
Gueorguiev M, Lecoeur C, Meyre D, Benzinou M, Mein C a, Hinney A, et al. Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity. Obesity (Silver Spring) [Internet]. 2009;17(4):745–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19165163
- There are currently no refbacks.
Copyright (c) 2018 Acta Medica Indonesiana