Obesity: hormonal regulation

Authors

  • Luísa Veiga Investigadora, Centro de Investigação em Genética e Metabolismo. Área Científica de Química, Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa. Lisboa, Portugal.

DOI:

https://doi.org/10.25758/set.1421

Keywords:

Obesity, Hormones, Adipose tissue, Gastrointestinal tract, Therapeutic approaches

Abstract

Obesity is considered by WHO a public health problem, as the number of overweight people worldwide is now 1.9 billion, out of which approximately 600 million are obese. This condition is correlated with a high risk of cardiovascular disease, diabetes, hypertension, and cancer. This pathology arises as a consequence of an imbalance between energy intake and energy expended. This imbalance can result from psychological, environmental, genetic, and metabolic factors, which are inducers of eating disorders such as increased food intake and a sedentary lifestyle. The regulation of energy balance results from a variety of afferent stimuli that are processed in the central nervous system, and efferent responses regulate appetite and satiety. Afferent impulses may occur by stimulating the vagus nerve or involving hormones released by adipose tissue (leptin, adiponectin, resistin, and visfatin) and the gastrointestinal tract (ghrelin, PYY, PP, GPL-1, and CCK). The response to the stimulus causes activation or inhibition of orexigenic neurons (NPY, AgRP) and/or anorexigenic neurons (POMC, CART), primarily expressed in the hypothalamus. While the activation of neurons that express AgRP and NPY increases appetite, the activation of neurons that express POMC provides satiety. Many studies have sought to understand these regulatory mechanisms of energy balance. However, the results are still not precise and arguably even contradictory. With this article, we intend to review the mechanisms of hormonal regulation involved in the pathogenesis of obesity, with particular emphasis on hormones produced in fat tissue, stomach, and intestine. As an epidemic of the XXI century because of its high prevalence and associated complications, it is crucial that obesity becomes the topic of further studies in order to find new therapeutic approaches. 

Downloads

Download data is not yet available.

References

World Health Organization. Obesity and overweight [Internet]. Geneva: WHO; 2016 [updated 2016 Jun]. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/

Simpson JA, MacInnis RJ, Peeters A, Hopper JL, Giles GG, English DR. A comparison of adiposity measures as predictors of all-cause mortality: the Melbourne Collaborative Cohort Study. Obesity (Silver Spring). 2007;15(4):994-1003.

Nowak A, Czkwianianc E. A contemporary approach to body mass regulation mechanisms. Przegla̜d Gastroenterol. 2016;11(2):73-7.

Näslund E, Hellström PM. Appetite signaling: from gut peptides and enteric nerves to brain. Physiol Behav. 2007;92(1-2):256-62.

Ricquier D. Fundamental mechanisms of thermogenesis. C R Biol. 2006;329(8):578-86.

Ahima RS. Adipose tissue as an endocrine organ. Obesity. 2006;14(S8):242S-9S.

World Health Organization. The world health report, 2000 - Health systems: improving performance. Geneva: WHO; 2000. ISBN 924156198X

Moehlecke M, Canani LH, Silva LO, Trindade MR, Friedman R, Leitão CB. Determinants of body weight regulation in humans. Arch Endocrinol Metab. 2016;60(2):152-62.

Peruzzo B, Pastor FE, Blázquez JL, Schöbitz K, Peláez B, Amat P, et al. A second look at the barriers of the medial basal hypothalamus. Exp Brain Res. 2000;132(1):10-26.

Woods SC, D’Alessio DA. Central control of body weight and appetite. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S37-50.

Damiani D, Damiani D. Sinalização cerebral do apetite [Appetite brain sinalization]. Rev Bras Clin Med São Paulo. 2011;9(2):138-45. Portuguese

Shuster A, Patlas M, Pinthus JH, Mourtzakis M. The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radiol. 2012;85(1009):1-10.

Waki H, Tontonoz P. Endocrine functions of adipose tissue. Annu Rev Pathol. 2007;2:31-56.

Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277-359.

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425-32.

Geffroy S, De Vos P, Staels B, Duban B, Auwerx J, de Martinville B. Localization of the human OB gene (OBS) to chromosome 7q32 by fluorescence in situ hybridization. Genomics. 1995;28(3):603-4.

Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007;8(1):21-34.

Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995;1(11):1155-61.

Mantzoros CS, Flier JS, Rogol AD. A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab. 1997;82(4):1066-70.

Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394(6696):897-901.

Park HY, Kwon HM, Lim HJ, Hong BK, Lee JY, Park BE, et al. Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro. Exp Mol Med. 2001;33(2):95-102.

Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol. 2000;68(4):437-46.

Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111(3):305-17.

Rodrigues AM, Suplicy HL, Radominski RB. Controle neuroendócrino do peso corporal: implicações na gênese da obesidade [Neuroendocrine control of food intake: implications in the genesis of obesity. Arq Bras Endocrinol Metab. 2003;47(4):398-409. Portuguese

Nonogaki K. New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia. 2000;43(5):533-49.

Sousa M, Sousa M, Brás-Silva C, Leite-Moreira A. The role of leptin in the regulation of energy balance. Acta Med Port. 2009;22(3):291-8.

López M, Tovar S, Vázquez MJ, Williams LM, Diéguez C. Peripheral tissue-brain interactions in the regulation of food intake. Proc Nutr Soc. 2007;66(1):131-55.

Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903-8.

Anubhuti V, Arora S. Leptin and its metabolic interactions: an update. Diabetes Obes Metab. 2008;10(11):973-93.

Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol. 1998;8(6):335-8.

Pajvani UB, Du X, Combs TP, Berg AH, Rajala MW, Schulthess T, et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin: implications for metabolic regulation and bioactivity. J Biol Chem. 2003;278(11):9073-85.

Silva-Nunes J, Duarte L, Veiga L, Melão A, Brito M, Malheiro F. Anthropometric determinants of adiponectin levels in obese and non obese premenopausal women. Endocr Abstr. 2009;20:P392.

Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762-9.

Ebrahimi-Mamaeghani M, Mohammadi S, Rafie Arefhosseini S, Fallah P, Bazi Z. Vascular health and risk management dovepress adiponectin as a potential biomarker of vascular disease. Vasc Health Risk Manag. 2015;11:55-70.

Yoon MJ, Lee GY, Chung J-J, Ahn YH, Hong SH, Kim JB. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha. Diabetes. 2006;55(9):2562-70.

Coles CA. Adipokines in healthy skeletal muscle and metabolic disease. Adv Exp Med Biol. 2016;900:133-60.

Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307-12.

Jamaluddin MS, Weakley SM, Yao Q, Chen C. Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br J Pharmacol. 2012;165(3):622-32.

Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, et al. Regulation of fasted blood glucose by resistin. Science. 2004;303(5661):1195-8.

Northcott JM, Yeganeh A, Taylor CG, Zahradka P, Wigle JT. Adipokines and the cardiovascular system: mechanisms mediating health and disease. Can J Physiol Pharmacol. 2012;90(8):1029-59.

Gallí M, Van Gool F, Rongvaux A, Andris F, Leo O. The nicotinamide phosphoribosyltransferase: a molecular link between metabolism, inflammation, and cancer. Cancer Res. 2010;70(1):8-11.

Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol. 1994;14(2):1431-7.

Chang Y-H, Chang D-M, Lin K-C, Shin S-J, Lee Y-J. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev. 2011;27(6):515-27.

Stastny J, Bienertova-Vasku J, Vasku A. Visfatin and its role in obesity development. Diabetes Metab Syndr. 2012;6(2):120-4.

Chang Y-C, Chang T-J, Lee W-J, Chuang L-M, Frayn KN, Karpe F, et al. The relationship of visfatin/pre-B-cell colony-enhancing factor/nicotinamide phosphoribosyltransferase in adipose tissue with inflammation, insulin resistance, and plasma lipids. Metabolism. 2010;59(1):93-9.

Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 2005;307(5708):426-30.

Berthoud H-R, Morrison C. The brain, appetite, and obesity. Annu Rev Psychol. 2008;59:55-92.

Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-7.

Delporte C. Structure and physiological actions of ghrelin. Scientifica (Cairo). 2013;2013:ID518909.

Seim I, Collet C, Herington AC, Chopin LK, Kojima M, Hosoda H, et al. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics. 2007;8:298.

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(3):387-96.

Olszewski PK, Li D, Grace MK, Billington CJ, Kotz CM, Levine AS. Neural basis of orexigenic effects of ghrelin acting within lateral hypothalamus. Peptides. 2003;24(4):597-602.

Tschöp M, Wawarta R, Riepl RL, Friedrich S, Bidlingmaier M, Landgraf R, et al. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest. 2001;24(6):RC19-21.

Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ, et al. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab. 2005;90(2):1055-60.

Asakawa A, Inui A, Fujimiya M, Sakamaki R, Shinfuku N, Ueta Y, et al. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut. 2005;54(1):18-24.

Delhanty PJ, Neggers SJ, van der Lely AJ. Des-acyl ghrelin: a metabolically active peptide. Endocr Dev. 2013;25:112-21.

Pacifico L, Poggiogalle E, Costantino F, Anania C, Ferraro F, Chiarelli F, et al. Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome. Eur J Endocrinol. 2009;161(6):861-70.

Rehfeld JF, Ivy AC, Oldberg E, Harper AA, Raper HS, Jorpes JE, et al. Cholecystokinin. Best Pract Res Clin Endocrinol Metab. 2004;18(4):569-86.

Rehfeld JF, Sun G, Christensen T, Hillingsø JG. The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33. J Clin Endocrinol Metab. 2001;86(1):251-8.

CCK cholecystokinin [Homo sapiens (human)]: ID 885. Gene - NCBI; 2016 [updated 2016 Oct 31]. Available from: https://www.ncbi.nlm.nih.gov/gene/885

Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA. Cholecystokinin bioactivity in human plasma: molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest. 1985;75(4):1144-52.

Harrold JA, Dovey TM, Blundell JE, Halford JC. CNS regulation of appetite. Neuropharmacology. 2012;63(1):3-17.

Wank SA. Cholecystokinin receptors. Am J Physiol. 1995;269(5 Pt 1):G628-46.

Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, et al. Anxiety-related behaviors in cholecystokinin-A, B, and AB receptor gene knockout mice in the plus-maze. Neurosci Lett. 2002;335(2):115-8.

Chaudhri O, Small C, Bloom S. Gastrointestinal hormones regulating appetite. Philos Trans R Soc Lond B Biol Sci. 2006;361(1471):1187-209.

Geary N. Endocrine controls of eating: CCK, leptin, and ghrelin. Physiol Behav. 2004;81(5):719-33.

Gehlert DR. Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological implications. Proc Soc Exp Biol Med. 1998;218(1):7-22.

Hort Y, Baker E, Sutherland GR, Shine J, Herzog H. Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1. Genomics. 1995;26(1):77-83.

Grandt D, Schimiczek M, Beglinger C, Layer P, Goebell H, Eysselein VE, et al. Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept. 1994;51(2):151-9.

Blomqvist AG, Herzog H. Y-receptor subtypes: how many more? Trends Neurosci. 1997;20(7):294-8.

Keire DA, Mannon P, Kobayashi M, Walsh JH, Solomon TE, Reeve JR. Primary structures of PYY, [Pro(34)]PYY, and PYY-(3-36) confer different conformations and receptor selectivity. Am J Physiol Gastrointest Liver Physiol. 2000;279(1):G126-31.

le Roux CW, Ghatei MA, Gibbs JSR, Bloom SR. The putative satiety hormone PYY is raised in cardiac cachexia associated with primary pulmonary hypertension. Heart. 2005;91(2):241-2.

Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 2003;349(10):941-8.

Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology. 1985;89(5):1070-7.

Chaudhri O, Small C, Bloom S. Gastrointestinal hormones regulating appetite. Philos Trans R Soc Lond B Biol Sci. 2006;361(1471):1187-209.

Track NS, McLeod RS, Mee AV. Human pancreatic polypeptide: studies of fasting and postprandial plasma concentrations. Can J Physiol Pharmacol. 1980;58(12):1484-9.

Cummings DE, Overduin J. Gastrointestinal regulation of food intake. J Clin Invest. 2007;117(1):13-23.

Banks WA, Kastin AJ, Jaspan JB. Regional variation in transport of pancreatic polypeptide across the blood-brain barrier of mice. Pharmacol Biochem Behav. 1995;51(1):139-47.

Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G, Fujimiya M, et al. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology. 2003;124(5):1325-36.

Zipf WB, O’Dorisio TM, Cataland S, Sotos J. Blunted pancreatic polypeptide responses in children with obesity of Prader-Willi syndrome. J Clin Endocrinol Metab. 1981;52(6):1264-6.

Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, et al. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab. 2003;88(8):3989-92.

Hameed S, Dhillo WS, Bloom SR. Gut hormones and appetite control. Oral Dis. 2009;15(1):18-26.

Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC. Exon duplication and divergence in the human preproglucagon gene. Nature. 1983;304(5924):368-71.

Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3(3):153-65.

Orskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ. Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes. 1994;43(4):535-9.

Edvell A, Lindström P. Initiation of increased pancreatic islet growth in young normoglycemic mice (Umeå +/?). Endocrinology. 1999;140(2):778-83.

Verdich C, Toubro S, Buemann B, Lysgård Madsen J, Juul Holst J, Astrup A. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety: effect of obesity and weight reduction. Int J Obes Relat Metab Disord. 2001;25(8):1206-14.

Vilsbøll T, Krarup T, Sonne J, Madsbad S, Vølund A, Juul AG, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003;88(6):2706-13.

Näslund E, King N, Mansten S, Adner N, Holst JJ, Gutniak M, et al. Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects. Br J Nutr. 2004;91(3):439-46.

Ghatei MA, Uttenthal LO, Christofides ND, Bryant MG, Bloom SR. Molecular forms of human enteroglucagon in tissue and plasma: plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract. J Clin Endocrinol Metab. 1983;57(3):488-95.

Pocai A. Unraveling oxyntomodulin, GLP1's enigmatic brother. J Endocrinol. 2012;215(3):335-46.

Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, et al. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003;88(10):4696-701.

Schepp W, Dehne K, Riedel T, Schmidtler J, Schaffer K, Classen M. Oxyntomodulin: a cAMP-dependent stimulus of rat parietal cell function via the receptor for glucagon-like peptide-1 (7-36)NH2. Digestion. 1996;57(6):398-405.

Maida A, Lovshin JA, Baggio LL, Drucker DJ. The glucagon-like peptide-1 receptor agonist oxyntomodulin enhances beta-cell function but does not inhibit gastric emptying in mice. Endocrinology. 2008;149(11):5670-8.

Pocai A. Action and therapeutic potential of oxyntomodulin. Mol Metab. 2014;3(3):241-51.

Baggio LL, Huang Q, Brown TJ, Drucker DJ. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology. 2004;127(2):546-58.

Published

2022-09-06

Issue

Section

Artigos de Revisão

How to Cite

Obesity: hormonal regulation. (2022). Saúde & Tecnologia, 16, 05-15. https://doi.org/10.25758/set.1421