Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Leptin Gene and Leptin Receptor Gene Polymorphisms Are Associated with Sweet Preference and Obesity

Abstract

Leptin is an adipocyte-secreted hormone that regulates food intake and body weight, and that was recently reported to suppress sweet sensitivity in an animal model. We investigated the associations among sweet preference, obesity, and polymorphisms of the leptin gene (LEP) or leptin receptor gene (LEPR). A total of 3,653 residents randomly selected from among the citizens of Suita City, Osaka, Japan were enlisted as subjects, in whom we investigated sweet preference, clinical characteristics, including obesity and serum leptin level, and the polymorphisms of LEP and LEPR (G-2548A and A19G for LEP; R109K, R223Q, and rs3790439 for LEPR). We determined the associations among the parameters using logistic regression analysis, in order to consider potential confounding factors for sweet preference and/or obesity. The LEP A19G and LEPR R109K polymorphisms were associated with sweet preference, whereas the serum leptin level was not. Further, the LEPR 109KK genotype was found to be associated with obesity along with sweet preference. In conclusion, our results are the first to show associations of LEP and LEPR polymorphisms with sweet preference, and may provide useful information for diagnosis and treatment of lifestyle-related diseases.

References

  1. 1

    Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG : Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 2006; 368: 666–678.

    Article  Google Scholar 

  2. 2

    Friedman JM, Halaas JL : Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–770.

    CAS  Article  Google Scholar 

  3. 3

    Mantzoros CS : The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 1999; 130: 671–680.

    CAS  Article  Google Scholar 

  4. 4

    Tartaglia LA : The leptin receptor. J Biol Chem 1997; 272: 6093–6096.

    CAS  Article  Google Scholar 

  5. 5

    Paracchini V, Pedotti P, Taioli E : Genetics of leptin and obesity: a HuGE review. Am J Epidemiol 2005; 162: 101–114.

    Article  Google Scholar 

  6. 6

    Thompson DB, Ravussin E, Bennett PH, Bogardus C : Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Hum Mol Genet 1997; 6: 675–679.

    CAS  Article  Google Scholar 

  7. 7

    Lakka TA, Rankinen T, Weisnagel SJ, et al: Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals. The HERITAGE family study. Diabetes 2004; 53: 1603–1608.

    CAS  Article  Google Scholar 

  8. 8

    Park KS, Shin HD, Park BL, et al: Polymorphisms in the leptin receptor (LEPR)—putative association with obesity and T2DM. J Hum Genet 2006; 51: 85–91.

    CAS  Article  Google Scholar 

  9. 9

    Matsuoka N, Ogawa Y, Hosoda K, et al: Human leptin receptor gene in obese Japanease subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity. Diabetologia 1997; 40: 1204–1210.

    CAS  Article  Google Scholar 

  10. 10

    Loos RJ, Rankinen T, Chagnon Y, Tremblay A, Perusse L, Bouchard C : Polymorphisms in the leptin and leptin receptor genes in relation to resting metabolic rate and respiratory quotient in the Quebec Family Study. Int J Obes 2006; 30: 183–190.

    CAS  Article  Google Scholar 

  11. 11

    Kawai K, Sugimoto K, Nakashima K, Miura H, Ninomiya Y : Leptin as a modulator of sweet taste sensitivities in mice. Proc Natl Acad Sci U S A 2000; 97: 11044–11049.

    CAS  Article  Google Scholar 

  12. 12

    de Luca C, Kowalski TJ, Zhang Y, et al: Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J Clin Invest 2005; 115: 3484–3493.

    CAS  Article  Google Scholar 

  13. 13

    Shigemura N, Ohta R, Kusakabe Y, et al: Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures. Endocrinology 2004; 145: 839–847.

    CAS  Article  Google Scholar 

  14. 14

    de Krom M, van der Schouw YT, Hendriks J, et al: Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns. Diabetes 2007; 56: 276–280.

    CAS  Article  Google Scholar 

  15. 15

    Bartoshuk LM, Duffy VB, Hayes JE, Moskowitz HR, Snyder DJ : Psychophysics of sweet and fat perception in obesity: problems, solutions and new perspectives. Philos Trans R Soc Lond B Biol Sci 2006; 361: 1137–1148.

    Article  Google Scholar 

  16. 16

    Karlin S, Cameron EC, Chakraborty R : Path analysis in genetic epidemiology: a critique. Am J Hum Genet 1983; 35: 695–732.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Wang TN, Huang MC, Chang WT, et al: G-2548A polymorphism of the leptin gene is correlated with extreme obesity in Taiwanese aborigines. Obesity 2006; 14: 183–187.

    CAS  Article  Google Scholar 

  18. 18

    Mammes O, Betoulle D, Aubert R, Herbeth B, Siest G, Fumeron F : Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight. Ann Hum Genet 2000; 64: 391–394.

    CAS  Article  Google Scholar 

  19. 19

    Le Stunff C, Le Bihan C, Schork NJ, Bougneres P : A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls. Diabetes 2000; 49: 2196–2200.

    CAS  Article  Google Scholar 

  20. 20

    Bernhardt SJ, Naim M, Zehavi U, Lindemann B : Changes in IP3 and cytosolic Ca2+ in response to sugars and non-sugar sweeteners in transduction of sweet taste in the rat. J Physiol 1996; 490: 325–336.

    CAS  Article  Google Scholar 

  21. 21

    Lindemann B : Taste reception. Physiol Rev 1996; 76: 719–766.

    CAS  Article  Google Scholar 

  22. 22

    Harvey J, Ashford ML : Insulin occludes leptin activation of ATP-sensitive K+ channels in rat CRI-G1 insulin secreting cells. J Physiol 1998; 510: 47–61.

    CAS  Article  Google Scholar 

  23. 23

    Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford ML : Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 1997; 390: 521–525.

    CAS  Article  Google Scholar 

  24. 24

    Freidman JM, Halaas JL : Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–770.

    Article  Google Scholar 

  25. 25

    Tartaglia LA, Dembski M, Weng X, et al: Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83: 1263–1271.

    CAS  Article  Google Scholar 

  26. 26

    Fong TM, Huang RR, Tota MR, et al: Localization of leptin binding domain in the leptin receptor. Mol Pharmacol 1998; 53: 234–240.

    CAS  Article  Google Scholar 

  27. 27

    Shigematsu Y, Norimatsu S, Ohtsuka T, Okayama H, Higaki J : Sex-related differences in the relations of insulin resistance and obesity to left ventricular hypertrophy in Japanese hypertensive patients. Hypertens Res 2006; 29: 499–504.

    CAS  Article  Google Scholar 

  28. 28

    Sakurai M, Miura K, Takamura T, et al: Gender differences in the association between anthropometric indices of obesity and blood pressure in Japanese. Hypertens Res 2006; 29: 75–80.

    Article  Google Scholar 

  29. 29

    Fujiwara T, Saitoh S, Takagi S, et al: Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia. Hypertens Res 2005; 28: 665–670.

    Article  Google Scholar 

  30. 30

    Takeuchi H, Saitoh S, Takagi S, et al: Metabolic syndrome and cardiac disease in Japanese men: applicability of the concept of metabolic syndrome defined by the National Cholesterol Education Program-Adult Treatment Panel III to Japanese men—the Tanno and Sobetsu Study. Hypertens Res 2005; 28: 203–208.

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Takayuki Morisaki.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mizuta, E., Kokubo, Y., Yamanaka, I. et al. Leptin Gene and Leptin Receptor Gene Polymorphisms Are Associated with Sweet Preference and Obesity. Hypertens Res 31, 1069–1077 (2008). https://doi.org/10.1291/hypres.31.1069

Download citation

Keywords

  • leptin
  • genetic polymorphism
  • obesity
  • taste

Further reading

Search

Quick links