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Sweet-Taste Receptor Signaling Network and Low-Calorie Sweeteners

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Sweeteners

Part of the book series: Reference Series in Phytochemistry ((RSP))

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Abstract

Over the past decades, low-calorie sweeteners (LCSs) have emerged as the main source of sweetening food products and beverages. Evidences suggest mixed effects of LCSs intake. In addition, there is a paucity of data on long-term health outcomes of LCSs intake as well as their usefulness in certain groups of the population (e.g., pregnant women, children, and the elderly). Moreover, available unbiased studies conducted to date are fairly scanty, thereby restraining far-reaching conclusions. LCSs are biomolecules with cognate cellular receptors ubiquitously localized in many organs and tissues of the body. The T1R2-T1R3 receptor heterodimer is one of the widely known receptors of LCSs. Upon activation by LCSs, T1R2-T1R3 signals downstream that result in several cellular responses that characterize the biochemical and physiological effects of LCSs. In the gut, for instance, signaling of LCSs may be mediated via humoral and neural mechanisms (involving the gut-brain axis, gut-adipose tissue axis, gut-adipose tissue-brain triangle, gut-pancreas-adipose tissue or entero-adipo-insular triangle, gut-brain-adipose tissue triangle) influence obesity, overweight, appetite, satiety, cognition, and memory. Several interconnected signaling pathways are important in modulating the physiological outcomes of LCS intake. In this chapter, we discuss the signaling mechanisms of LCSs, and their relationship to metabolism, obesity, weight gain, satiety, appetite, cognition, and memory.

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Abbreviations

AC:

Adenylate cyclase

ACTH:

Adrenocorticotropic Hormone

AgRP:

Agouti-related protein

AMPK:

AMP-activated protein kinase

AP:

Area postrema

ATP:

Adenosine triphosphate

CALHM1:

Calcium homeostasis modulator 1

CAMK:

Calmodulin-dependent protein kinase

cAMP:

Cyclic adenosine monophosphate

CART:

Cocaine and amphetamine regulated transcript

CREB:

cAMP-related element binding protein

CRH:

Corticotropin releasing hormone

DMN:

Dorsomotor nucleus

GABA:

Gamma amino butyric acid

GLP-1:

Glucagon-like peptide-1

GLUT:

GLUcose Transporter

IP3:

1,4,5-inositol trisphosphate

Low-calorie sweeteners:

LCSs

MC4R:

Melanocortin receptor type-4

mTOR:

Mammalian target of rapamycin

mTORC1:

Mammalian target of rapamycin 1

NPY:

Neuropeptide Y

NTS:

Nucleus tractus solitarius

Ob-Rb:

Adiposity (obesity) receptor type b

PDE:

Phosphodiesterase

PI3K:

Phosphoinositide-3-kinase

PKB:

Protein kinase B

PLCβ:

Phospholipase Cβ

POMC:

Proopiomelanocortin

PVN:

Paraventricular nucleus

PYY:

Peptide YY

SGLT:

Sodium-dependent glucose cotransporter

T1R2-T1R3:

Sweet-taste receptor heterodimer

TRH:

Thyrotropin releasing hormone

TRPM5:

Transient receptor potential cation channel, subfamily M, member 5

α-MSH:

Alpha-melanin-stimulating hormone

References

  1. Weihrauch MR, Diehl V (2004) Artificial sweeteners – do they bear a carcinogenic risk? Ann Oncol 15:1460–1465

    Article  CAS  Google Scholar 

  2. Kant R (2005) Sweet proteins – potential replacement for artificial low calorie sweeteners. Nutr J 4:5

    Article  Google Scholar 

  3. Roberts A (2016) The safety and regulatory process for low calorie sweeteners in the United States. Physiol Behav. doi:10.1016/j.physbeh.2016.02.039

    Google Scholar 

  4. Grembecka M (2015) Natural sweeteners in a human diet. Rocz Panstw Zakl Hig 66(3):195–202

    Google Scholar 

  5. Miller PE, Perez V (2014) Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr 100:765–777

    Article  CAS  Google Scholar 

  6. Gardner C (2014) Non-nutritive sweeteners: evidence for benefit vs. risk. Curr Opin Lipidol 25(1):80–84

    Article  CAS  Google Scholar 

  7. Fitch C, Keim KS, Academy of Nutrition and Dietetics (2012) Position of the academy of nutrition and dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 112(5):739–758

    Article  Google Scholar 

  8. Piernas C, Mendez MA, Ng SW, Gordon-Larsen P, Popkin BM (2014) Low-calorie- and calorie-sweetened beverages: diet quality, food intake, and purchase patterns of US household consumers. Am J Clin Nutr 99(3):567–577

    Article  CAS  Google Scholar 

  9. Sylvetsky AC, Rother KI (2016) Trends in the consumption of low-calorie sweeteners. Physiol Behav. doi:10.1016/j.physbeh.2016.03.030

    Google Scholar 

  10. Foreyt J, Kleinman R, Brown RJ, Lindstrom R (2012) the use of low-calorie sweeteners by children: implications for weight management. J Nutr 142:1155S–1162S

    Article  CAS  Google Scholar 

  11. Raben A, Richelsen B (2012) Artificial sweeteners: a place in the field of functional foods? Focus on obesity and related metabolic disorders. Curr Opin Clin Nutr Metab Care 15(6):597–604

    Article  CAS  Google Scholar 

  12. Shankar P, Ahuja S, Sriram K (2013) Non-nutritive sweeteners: review and update. Nutrition 29(11–12):1293–1299

    Article  CAS  Google Scholar 

  13. Anderson GH, Foreyt J, Sigman-Grant M, Allison DB (2012) The use of low-calorie sweeteners by adults: impact on weight management. J Nutr. 142(6):1163S–1169S

    Article  CAS  Google Scholar 

  14. Gibson S, Drewnowski A, Hill J, Raben AB, Tuorila H, Widström E (2014) Consensus statement on benefits of low-calorie sweeteners. Nutr Bull 39:386–389

    Article  Google Scholar 

  15. Mennella JA, Pepino MY, Reed DR (2005) Genetic and environmental determinants of bitter perception and sweet preferences. Pediatrics 115(2):e216–e222

    Article  Google Scholar 

  16. Tepper BJ, White EA, Koelliker Y, Lanzara C, d'Adamo P, Gasparini P (2009) Genetic variation in taste sensitivity to 6-n-propylthiouracil and its relationship to taste perception and food selection. Ann N Y Acad Sci 1170:126–139

    Article  CAS  Google Scholar 

  17. Ventura AK, Mennella JA (2011) Innate and learned preferences for sweet taste during childhood. Curr Opin Clin Nutr Metab Care 14(4):379–384

    Article  Google Scholar 

  18. Liem DG, de Graaf C (2004) Sweet and sour preferences in young children and adults: role of repeated exposure. Physiol Behav 83(3):421–429

    Article  CAS  Google Scholar 

  19. El-Sohemy A, Stewart L, Khataan N, Fontaine-Bisson B, Kwong P, Ozsungur S, Cornelis MC (2007) Nutrigenomics of taste – impact on food preferences and food production. Forum Nutr 60:176–182

    Article  CAS  Google Scholar 

  20. Margolskee RF (2002) Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem 277:1–4

    Article  CAS  Google Scholar 

  21. McLaughlin SK, McKinnon PJ, Robichon A, Spickofsky N, Margolskee RF (1993) Gustducin and transducin: a tale of two G proteins. Ciba Found Symp 179:186–200

    CAS  Google Scholar 

  22. Lindemann B (1996) Chemoreception: tasting the sweet and the bitter. Curr Biol 6(10):1234–1237

    Article  CAS  Google Scholar 

  23. Margolskee RF (1993) The molecular biology of taste transduction. Bioessays 15(10):645–650

    Article  CAS  Google Scholar 

  24. Depoortere I (2014) Taste receptors of the gut: emerging roles in health and disease. Gut 63(1):179–190

    Article  CAS  Google Scholar 

  25. Ohkuri T, Yasumatsu K, Horio N, Jyotaki M, Margolskee RF, Ninomiya Y (2009) Multiple sweet receptors and transduction pathways revealed in knockout mice by temperature dependence and gurmarin sensitivity. Am J Physiol – Regul, Integr Comp Physiol 296(4):R960–R971

    Article  CAS  Google Scholar 

  26. Wright EM, Turk E (2004) The sodium/glucose cotransport family SLC5. Pflugers Arch 447(5):510–518

    Article  CAS  Google Scholar 

  27. Harada N, Inagaki N (2012) Role of sodium-glucose transporters in glucose uptake of the intestine and kidney. J Diab Invest 3(4):352–353

    Article  CAS  Google Scholar 

  28. Takata K, Hirano H, Kasahara M (1997) Transport of glucose across the blood-tissue barriers. Int Rev Cytol 172:1–53

    Article  CAS  Google Scholar 

  29. Janssen S, Depoortere I (2013) Nutrient sensing in the gut: new roads to therapeutics? Trends in Endocrin Metab 24(2):92–100

    Article  CAS  Google Scholar 

  30. Folmes CD, Lopaschuk GD (2007) Role of malonyl-CoA in heart disease and the hypothalamic control of obesity. Cardiovasc Res 73(2):278–287

    Article  CAS  Google Scholar 

  31. Riediger T, Zuend D, Becskei C, Lutz TA (2004) The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis. Am J Physiol Regul Integr Comp Physiol 286(1):R114–R122

    Article  CAS  Google Scholar 

  32. Riediger T (2012) The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance. Proc Nutr Soc 71(4):463–477

    Article  CAS  Google Scholar 

  33. Valassi E, Scacchi M, Cavagnini F (2008) Neuroendocrine control of food intake. Nutr Metab Cardiovas Dis 18:158–168

    Article  CAS  Google Scholar 

  34. Cui H, Cai F, Belsham DD (2005) Anorexigenic hormones leptin, insulin, and alpha-melanocyte-stimulating hormone directly induce neurotensin (NT) gene expression in novel NT-expressing cell models. J Neurosci 25(41):9497–9506

    Article  CAS  Google Scholar 

  35. Wellman PJ (2000) Norepinephrine and the control of food intake. Nutrition 16(10):837–842

    Article  CAS  Google Scholar 

  36. Hanusch-Enserer U, Roden M (2005) News in gut-brain communication: a role of peptide YY (PYY) in human obesity and following bariatric surgery? Eur J Clin Invest 35(7):425–430

    Article  CAS  Google Scholar 

  37. Watterson KR, Bestow D, Gallagher J, Hamilton DL, Ashford FB, Meakin PJ, Ashford ML (2013) Anorexigenic and orexigenic hormone modulation of mammalian target of rapamycin complex 1 activity and the regulation of hypothalamic agouti-related protein mRNA expression. Neurosignals 21(1–2):28–41

    Article  CAS  Google Scholar 

  38. Yoshida R, Niki M, Jyotaki M, Sanematsu K, Shigemura N, Ninomiya Y (2013) Modulation of sweet responses of taste receptor cells. Sem in Cell Dev Biol 24(3):226–231

    Article  CAS  Google Scholar 

  39. Gil-Campos M, Aguilera CM, Cañete R, Gil A (2006) Ghrelin: a hormone regulating food intake and energy homeostasis. Br J Nutr 96(2):201–226

    Article  CAS  Google Scholar 

  40. Ghamari-Langroudi M, Colmers WF, Cone RD (2005) PYY3–36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors. Cell Metab 2(3):191–199

    Article  CAS  Google Scholar 

  41. Druce M, Bloom SR (2006) The regulation of appetite. Arch Dis Child. 91(2):183–187

    Article  CAS  Google Scholar 

  42. Welcome MO, Pereverzev VA (2013) A mini-review of the mechanisms of glucose memory enhancement. Int J Med Pharm Sci 4(1):17–30

    Google Scholar 

  43. Welcome MO, Mastorakis NE, Pereverzev VA (2015) Sweet taste receptor signaling network: possible implication for cognitive functioning. Neurol Res Int (Hindawi Publishing Corporation), Article ID 606479, 13 pages. doi:10.1155/2015/606479. https://www.hindawi.com/journals/nri/2015/606479/

  44. Ren X, Zhou L, Terwilliger R, Newton SS, de Araujo IE (2009) Sweet taste signaling functions as a hypothalamic glucose sensor. Front Integr Neurosci 3:12

    Article  Google Scholar 

  45. de Araujo IE, Ren X, Ferreira JG (2010) Metabolic sensing in brain dopamine systems. Res Prob Cell Different 52:69–86

    Article  Google Scholar 

  46. Hurtado-Carneiro V, Sanz C, Roncero I, Vazquez P, Blazquez E, Alvarez E (2012) Glucagon-like peptide 1 (GLP-1) can reverse AMP-activated protein kinase (AMPK) and S6 kinase (P70S6K) activities induced by fluctuations in glucose levels in hypothalamic areas involved in feeding behavior. Mol Neurobiol 45(2):348–361

    Article  CAS  Google Scholar 

  47. Xu J, Ji J, Yan XH (2012) Cross-talk between AMPK and mTOR in regulating energy balance. Crit Rev Food Sci Nutr 52(5):373–381

    Article  CAS  Google Scholar 

  48. Ehninger D, de Vries PJ, Silva AJ (2009) From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis. J Intellect Disabil Res 53(10):838–851

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Basic Medical Sciences, Madonna University, Elele, Rivers State, Nigeria

    Menizibeya O. Welcome

  2. World Scientific and Engineering Society and Academy, Athens, Greece

    Menizibeya O. Welcome & Nikos E. Mastorakis

  3. Technical University of Sofia, Sofia, Bulgaria

    Nikos E. Mastorakis

  4. Department of Normal Physiology, Belarusian State Medical University, Pr., Dzerjinsky, 83, 220116, Minsk, Belarus

    Vladimir A. Pereverzev

Authors
  1. Menizibeya O. Welcome
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  2. Nikos E. Mastorakis
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  3. Vladimir A. Pereverzev
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Corresponding author

Correspondence to Menizibeya O. Welcome .

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Editors and Affiliations

  1. Faculty of Pharmaceutical Sciences, University of Bordeaux, Bordeaux, France

    Jean-Michel Mérillon

  2. Botany Department, M.L. Sukhadia University, Udaipur, India

    Kishan Gopal Ramawat

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Welcome, M.O., Mastorakis, N.E., Pereverzev, V.A. (2018). Sweet-Taste Receptor Signaling Network and Low-Calorie Sweeteners. In: Mérillon, JM., Ramawat, K. (eds) Sweeteners. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-27027-2_25

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