The obesogenic effect of high fructose exposure during early development

Abstract

Obesogens are compounds that disrupt the function and development of adipose tissue or the normal metabolism of lipids, leading to an increased risk of obesity and associated diseases. Evidence for the adverse effects of industrial and agricultural obesogens, such as tributyltin, bisphenol A and other organic pollutants is well-established. Current evidence suggests that high maternal consumption of fat promotes obesity and increased metabolic risk in offspring, but less is known about the effects of other potential nutrient obesogens. Widespread increase in dietary fructose consumption over the past 30 years is associated with chronic metabolic and endocrine disorders and alterations in feeding behaviour that promote obesity. In this Perspectives, we examine the evidence linking high intakes of fructose with altered metabolism and early obesity. We review the evidence suggesting that high fructose exposure during critical periods of development of the fetus, neonate and infant can act as an obesogen by affecting lifelong neuroendocrine function, appetite control, feeding behaviour, adipogenesis, fat distribution and metabolic systems. These changes ultimately favour the long-term development of obesity and associated metabolic risk.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Links between obesity and fructose exposure during critical developmental periods.

References

  1. 1

    Loos, R. J. Recent progress in the genetics of common obesity. Br. J. Clin. Pharmacol. 68, 811–829 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

    Blumberg, B. Obesogens, stem cells and the maternal programming of obesity. J. Dev. Orig. Health Dis. 2, 3–8 (2011).

    CAS  PubMed  Google Scholar 

  3. 3

    Janesick, A. & Blumberg, B. in Obesity before birth Vol. 30 Ch. 19 (ed. Lustig, R. H.) 383–399 (Springer, 2011).

    Google Scholar 

  4. 4

    Janesick, A. & Blumberg, B. Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res. C. Embryo Today 93, 34–50 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    La Merrill, M. & Birnbaum, L. S. Childhood obesity and environmental chemicals. Mt Sinai J. Med. 78, 2–48 (2011).

    Google Scholar 

  6. 6

    Heindel, J. J. in Obesity before birth Vol. 30 Ch. 17 (ed. Lustig, R. H.) 355–366 (Springer, 2011).

    Google Scholar 

  7. 7

    Newbold, R. R. in Obesity before birth Vol. 30 Ch. 18 (ed. Lustig, R. H.) 367–382 (Springer, 2011).

    Google Scholar 

  8. 8

    Newbold, R. R., Padilla-Banks, E. & Jefferson, W. N. Environmental oestrogens and obesity. Mol. Cell. Endocrinol. 304, 84–89 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Rubin, B. S., Murray, M. K., Damassa, D. A., King, J. C. & Soto, A. M. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ. Health Perspect. 109, 675–80 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Rubin, B. S. Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. J. Steroid Biochem. Mol. Biol. 127, 27–34 (2011).

    CAS  PubMed  Google Scholar 

  11. 11

    Grün, F. et al. Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol. Endocrinol. 20, 2141–2155 (2006).

    PubMed  Google Scholar 

  12. 12

    Hines, E. P. et al. Phenotypic dichotomy following developmental exposure to perfluorooctanoic acid (PFOA) in female CD-1 mice: low doses induce elevated serum leptin and insulin, and overweight in mid-life. Mol. Cell. Endocrinol. 304, 97–105 (2009).

    CAS  PubMed  Google Scholar 

  13. 13

    Stahlhut, R. W., van Wijgaarden, E., Dye, T. D., Cook, S. & Swan, S. H. Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ. Health Perspect. 115, 876–882 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Hatch, E. E. et al. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002. Environ. Health 7, 27 (2008).

    PubMed  PubMed Central  Google Scholar 

  15. 15

    Tang-Peronard, J. L., Andersen, H. R., Jensen, T. K. & Heitmann, B. L. Endocrine-disrupting chemicals and obesity development in humans: a review. Obes. Rev. 12, 622–636 (2011).

    CAS  PubMed  Google Scholar 

  16. 16

    Phillips, S. M. et al. Energy-dense snack food intake in adolescence: longitudinal relationship to weight and fatness. Obes. Res. 12, 461–472 (2004).

    PubMed  Google Scholar 

  17. 17

    Ludwig, D. S., Peterson, K. E. & Gortmaker, S. L. Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 357, 505–508 (2001).

    CAS  PubMed  Google Scholar 

  18. 18

    Berkey, C. S., Rockett, H. R., Field, A. E., Gillman, M. W. & Colditz, G. A. Sugar-added beverages and adolescent weight change. Obes. Res. 12, 778–788 (2004).

    PubMed  Google Scholar 

  19. 19

    Kant, A. K. Reported consumption of low-nutrient-density foods by American children and adolescents: nutritional and health correlates, NHANES III, 1988 to 1994. Arch. Paediatr. Adolesc. Med. 157, 789–796 (2003).

    Google Scholar 

  20. 20

    Welsh, J. A. et al. Overweight among low-income preschool children associated with the consumption of sweet drinks: Missouri, 1999–2002. Paediatrics 115, e223–e229 (2005).

    Google Scholar 

  21. 21

    Davis, J. N., Whalley, S. & Goran, M. I. Effects of breastfeeding and low sugar sweetened beverage intake on obesity prevalence in Hispanic toddlers. Am. J. Clin. Nutr. 95, 3–8 (2012).

    CAS  PubMed  Google Scholar 

  22. 22

    Forshee, R. A., Anderson, P. A. & Storey, M. L. Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis. Am. J. Clin. Nutr. 87, 1662–1671 (2008).

    CAS  PubMed  Google Scholar 

  23. 23

    Malik, V. S., Willett, W. C. & Hu, F. B. Sugar-sweetened beverages and BMI in children and adolescents: reanalyses of a meta-analysis. Am. J. Clin. Nutr. 89, 438–440 (2009).

    CAS  PubMed  Google Scholar 

  24. 24

    Reedy, J. & Krebs-Smith, S. M. Dietary sources of energy, solid fats, and added sugars among children and adolescents in the United States. J. Am. Diet. Assoc. 110, 1477–1484 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Marshall, R. O. & Kooi, E. R. Enzymatic conversion of D-glucose to D-fructose. Science 125, 648–649 (1957).

    CAS  PubMed  Google Scholar 

  26. 26

    Marriott, B. P., Cole, N. & Lee, E. National estimates of dietary fructose intake increased from 1977 to 2004 in the United States. J. Nutr. 139, 1228S–1235S (2009).

    CAS  PubMed  Google Scholar 

  27. 27

    Gross, L. S., Li, L., Ford, E. S. & Liu, S. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am. J. Clin. Nutr. 79, 774–779 (2004).

    CAS  PubMed  Google Scholar 

  28. 28

    Goran, M. I., Ulijaszek, S. J. & Ventura, E. E. High fructose corn syrup and diabetes prevalence: a global perspective. Glob. Public Health 8, 55–64 (2013).

    PubMed  Google Scholar 

  29. 29

    Le, M. T. et al. Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and haemodynamic responses in healthy subjects. Metabolism 61, 641–651 (2012).

    CAS  PubMed  Google Scholar 

  30. 30

    Hanover, L. M. & White, J. S. Manufacturing, composition, and applications of fructose. Am. J. Clin. Nutr. 58, 724S–732S (1993).

    CAS  PubMed  Google Scholar 

  31. 31

    Ventura, E. E., Davis, J. N. & Goran, M. I. Sugar content of popular sweetened beverages based on objective laboratory analysis: focus on fructose content. Obesity (Silver Spring) 19, 868–874 (2011).

    CAS  Google Scholar 

  32. 32

    Bray, G. A., Nielsen, S. J. & Popkin, B. M. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am. J. Clin. Nutr. 79, 537–543 (2004).

    CAS  PubMed  Google Scholar 

  33. 33

    Elliott, S. S., Keim, N. L., Stern, J. S., Teff, K. & Havel, P. J. Fructose, weight gain, and the insulin resistance syndrome. Am. J. Clin. Nutr. 76, 911–922 (2002).

    CAS  PubMed  Google Scholar 

  34. 34

    Gaby, A. R. Adverse effects of dietary fructose. Altern. Med. Rev. 10, 294–306 (2005).

    PubMed  Google Scholar 

  35. 35

    Lim, J. S., Mietus-Snyder, M., Valente, A., Schwarz, J. M. & Lustig, R. H. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat. Rev. Gastroenterol. Hepatol. 7, 251–264 (2010).

    CAS  PubMed  Google Scholar 

  36. 36

    Lustig, R. H. Fructose: metabolic, hedonic, and societal parallels with ethanol. J. Am. Diet. Assoc. 110, 1307–1321 (2010).

    CAS  PubMed  Google Scholar 

  37. 37

    Maersk, M. et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am. J. Clin. Nutr. 95, 283–289 (2012).

    CAS  PubMed  Google Scholar 

  38. 38

    Le, K. A. et al. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am. J. Clin. Nutr. 89, 1760–1765 (2009).

    CAS  PubMed  Google Scholar 

  39. 39

    Stanhope, K. L. et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J. Clin. Invest. 119, 1322–1334 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Cox, C. L. et al. Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein 4, and γ-glutamyl transferase activity in overweight/obese humans. Nutr. Metab. (Lond.) 9, 68 (2012).

    CAS  Google Scholar 

  41. 41

    Lin, W. T. et al. Effects on uric acid, body mass index and blood pressure in adolescents of consuming beverages sweetened with high-fructose corn syrup. Int. J. Obes. (Lond.) 37, 532–539 (2013).

    CAS  Google Scholar 

  42. 42

    Sievenpiper, J. L. et al. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann. Intern. Med. 156, 291–304 (2012).

    PubMed  Google Scholar 

  43. 43

    Lowndes, J. et al. The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters. Nutr. J. 11, 55 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Rippe, J. M. & Kris Etherton, P. M. Fructose, sucrose, and high fructose corn syrup: modern scientific findings and health implications. Adv. Nutr. 3, 739–740 (2012).

    PubMed  PubMed Central  Google Scholar 

  45. 45

    Aeberli, I. et al. Moderate amounts of fructose consumption impair insulin sensitivity in healthy young men: a randomized controlled trial. Diabetes Care 36, 150–156 (2013).

    CAS  PubMed  Google Scholar 

  46. 46

    Pagliassotti, M. J., Prach, P. A., Koppenhafer, T. A. & Pan, D. A. Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am. J. Physiol. 271, R1319–R1326 (1996).

    CAS  PubMed  Google Scholar 

  47. 47

    Thresher, J. S., Podolin, D. A., Wei, Y., Mazzeo, R. S. & Pagliassotti, M. J. Comparison of the effects of sucrose and fructose on insulin action and glucose tolerance. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, R1334–R1340 (2000).

    CAS  PubMed  Google Scholar 

  48. 48

    Pagliassotti, M. J. & Prach, P. A. Quantity of sucrose alters the tissue pattern and time course of insulin resistance in young rats. Am. J. Physiol. 269, R641–R646 (1995).

    CAS  PubMed  Google Scholar 

  49. 49

    Pagliassotti, M. J., Shahrokhi, K. A. & Moscarello, M. Involvement of liver and skeletal muscle in sucrose-induced insulin resistance: dose–response studies. Am. J. Physiol. 266, R1637–R1644 (1994).

    CAS  PubMed  Google Scholar 

  50. 50

    Shapiro, A. et al. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, R1370–R1375 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Pagliassotti, M. J., Gayles, E. C., Podolin, D. A., Wei, Y. & Morin, C. L. Developmental stage modifies diet-induced peripheral insulin resistance in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R66–R73 (2000).

    CAS  PubMed  Google Scholar 

  52. 52

    Horton, T. J., Gayles, E. C., Prach, P. A., Koppenhafer, T. A. & Pagliassotti, M. J. Female rats do not develop sucrose-induced insulin resistance. Am. J. Physiol. 272, R1571–R1576 (1997).

    CAS  PubMed  Google Scholar 

  53. 53

    Kanarek, R. B. & Orthen-Gambill, N. Differential effects of sucrose, fructose and glucose on carbohydrate-induced obesity in rats. J. Nutr. 112, 1546–1554 (1982).

    CAS  PubMed  Google Scholar 

  54. 54

    Hirsch, E., Dubose, C. & Jacobs, H. L. Overeating, dietary selection patterns and sucrose intake in growing rats. Physiol. Behav. 28, 819–828 (1982).

    CAS  PubMed  Google Scholar 

  55. 55

    Kanarek, R. B. & Marks-Kaufman, R. Developmental aspects of sucrose-induced obesity in rats. Physiol. Behav. 23, 881–885 (1979).

    CAS  PubMed  Google Scholar 

  56. 56

    Jurgens, H. et al. Consuming fructose-sweetened beverages increases body adiposity in mice. Obes. Res. 13, 1146–1156 (2005).

    PubMed  Google Scholar 

  57. 57

    Bocarsly, M. E., Powell, E. S., Avena, N. M. & Hoebel, B. G. High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels. Pharmacol. Biochem. Behav. 97, 101–106 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Teff, K. L. et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J. Clin. Endocrinol. Metab. 89, 2963–2972 (2004).

    CAS  PubMed  Google Scholar 

  59. 59

    Purnell, J. Q. et al. Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans. Diabetes Obes. Metab. 13, 229–234 (2011).

    CAS  PubMed  Google Scholar 

  60. 60

    Page, K. A. et al. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA 309, 63–70 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Cha, S. H., Wolfgang, M., Tokutake, Y., Chohnan, S. & Lane, M. D. Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake. Proc. Natl Acad. Sci. USA 105, 16871–16875 (2008).

    CAS  PubMed  Google Scholar 

  62. 62

    Bouret, S. G., Draper, S. J. & Simerly, R. B. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304, 108–110 (2004).

    CAS  PubMed  Google Scholar 

  63. 63

    Bouret, S. G. Role of early hormonal and nutritional experiences in shaping feeding behaviour and hypothalamic development. J. Nutr. 140, 653–657 (2010).

    CAS  PubMed  Google Scholar 

  64. 64

    Bouret, S. G. & Simerly, R. B. Minireview: Leptin and development of hypothalamic feeding circuits. Endocrinology 145, 2621–2626 (2004).

    CAS  PubMed  Google Scholar 

  65. 65

    McCurdy, C. E. et al. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J. Clin. Invest. 119, 323–335 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Lawlor, D. A. et al. Epidemiologic evidence for the fetal overnutrition hypothesis: findings from the mater-university study of pregnancy and its outcomes. Am. J. Epidemiol. 165, 418–424 (2007).

    PubMed  Google Scholar 

  67. 67

    Knight, B. et al. The impact of maternal glycaemia and obesity on early postnatal growth in a nondiabetic Caucasian population. Diabetes Care 30, 777–783 (2007).

    PubMed  Google Scholar 

  68. 68

    Kral, J. G. et al. Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years. Paediatrics 118, e1644–e1649 (2006).

    Google Scholar 

  69. 69

    Taylor, G. M., Alexander, F. E. & D'Souza, S. W. Interactions between fetal HLA-DQ alleles and maternal smoking influence birthweight. Paediatr. Perinat. Epidemiol. 20, 438–448 (2006).

    PubMed  Google Scholar 

  70. 70

    Malik, S., McGlone, F., Bedrossian, D. & Dagher, A. Ghrelin modulates brain activity in areas that control appetitive behaviour. Cell. Metab. 7, 400–409 (2008).

    CAS  PubMed  Google Scholar 

  71. 71

    Alzamendi, A., Castrogiovanni, D., Gaillard, R. C., Spinedi, E. & Giovambattista, A. Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother. Endocrinology 151, 4214–4223 (2010).

    CAS  PubMed  Google Scholar 

  72. 72

    Jen, K. L. C., Rochon, C., Zhong, S. & Whitcomb, L. Fructose and sucrose feeding during pregnancy and lactation in rats changes maternal and pup fuel metabolism. J. Nutr. 121, 1999–2005 (1991).

    CAS  PubMed  Google Scholar 

  73. 73

    Light, H. R., Tsanzi, E., Gigliotti, J., Morgan, K. & Tou, J. C. The type of caloric sweetener added to water influences weight gain, fat mass, and reproduction in growing Sprague-Dawley female rats. Exp. Biol. Med. (Maywood) 234, 651–661 (2009).

    CAS  Google Scholar 

  74. 74

    Rawana, S. et al. Low dose fructose ingestion during gestation and lactation affects carbohydrate metabolism in rat dams and their offspring. J. Nutr. 123, 2158–2165 (1993).

    CAS  PubMed  Google Scholar 

  75. 75

    Vickers, M. H., Clayton, Z. E., Yap, C. & Sloboda, D. M. Maternal fructose Intake during pregnancy and lactation alters placental growth and leads to sex-specific changes in fetal and neonatal endocrine function. Endocrinology 152, 1378–1387 (2011).

    CAS  PubMed  Google Scholar 

  76. 76

    Ghusain-Choueiri, A. A. & Rath, E. A. Effect of carbohydrate source on lipid metabolism in lactating mice and on pup development. Br. J. Nutr. 74, 821–831 (1995).

    CAS  PubMed  Google Scholar 

  77. 77

    Brion, M. J. et al. Maternal macronutrient and energy intakes in pregnancy and offspring intake at 10 y: exploring parental comparisons and prenatal effects. Am. J. Clin. Nutr. 91, 748–756 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Myers, K. P. & Sclafani, A. Development of learned flavour preferences. Dev. Psychobiol. 48, 380–388 (2006).

    PubMed  Google Scholar 

  79. 79

    Bayol, S. A., Farrington, S. J. & Stickland, N. C. A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring. Br. J. Nutr. 98, 843–851 (2007).

    CAS  PubMed  Google Scholar 

  80. 80

    Bayol, S. A., Simbi, B. H., Bertrand, J. A. & Sticklandm, N. C. Offspring from mothers fed a 'junk food' diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J. Physiol. 586, 3219–3230 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Jenness, R. The composition of human milk. Semin. Perinatol. 3, 225–239 (1979).

    CAS  PubMed  Google Scholar 

  82. 82

    Davidson, N. O. et al. Human intestinal glucose transporter expression and localization of GLUT5. Am. J. Physiol. 262, C795–C800 (1992).

    CAS  PubMed  Google Scholar 

  83. 83

    Burant, C. F. & Saxena, M. Rapid reversible substrate regulation of fructose transporter expression in rat small intestine and kidney. Am. J. Physiol. 267, G71–G79 (1994).

    CAS  PubMed  Google Scholar 

  84. 84

    Douard, V., Choi, H. I., Elshenawy, S., Lagunoff, D. & Ferraris, R. P. Developmental reprogramming of rat GLUT5 requires glucocorticoid receptor translocation to the nucleus. J. Physiol. 586, 3657–3673 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Douard, V. & Ferraris, R. P. Regulation of the fructose transporter GLUT5 in health and disease. Am. J. Physiol. Endocrinol. Metab. 295, E227–E237 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Holmberg, N. G., Kaplan, B., Karvonen, M. J., Lind, J. & Malm, M. Permeability of human placenta to glucose, fructose, and xylose. Acta Physiol. Scand. 36, 291–299 (1956).

    CAS  PubMed  Google Scholar 

  87. 87

    Hagerman, D. D. & Villee, C. A. The transport of fructose by human placenta. J. Clin. Invest. 31, 911–913 (1952).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88

    Du, L. & Heaney, A. P. Regulation of adipose differentiation by fructose and Glut5. Mol. Endocrinol. 26, 1773–1782 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89

    Sandoval, D., Cota, D. & Seeley, R. J. The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation. Annu. Rev. Physiol. 70, 513–535 (2008).

    CAS  PubMed  Google Scholar 

  90. 90

    Elmquist, J. K., Coppari, R., Balthasar, N., Ichinose, M. & Lowell, B. B. Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J. Comp. Neurol. 493, 63–71 (2005).

    CAS  PubMed  Google Scholar 

  91. 91

    Kirk, S. L. et al. Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring. PLoS ONE 4, e5870 (2009).

    PubMed  PubMed Central  Google Scholar 

  92. 92

    Glavas, M. M. et al. Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet. Endocrinology 151, 1598–1610 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Kanayama, T., Kobayashi, N., Mamiya, S., Nakanishi, T. & Nishikawa, J. Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor γ/retinoid X receptor pathway. Mol. Pharmacol. 67, 766–774 (2005).

    CAS  PubMed  Google Scholar 

  94. 94

    Kirchner, S., Kieu, T., Chow, C., Casey, S. & Blumberg, B. Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Mol. Endocrinol. 24, 526–539 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Li, X., Ycaza, J. & Blumberg, B. The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor γ to induce adipogenesis in murine 3T3-L1 preadipocytes. J. Steroid Biochem. Mol. Biol. 127, 9–15 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96

    Chamorro-Garcia, R. et al. Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal obesogen tributyltin in mice. Environ. Health Perspect. 121, 359–366 (2013).

    PubMed  PubMed Central  Google Scholar 

  97. 97

    Grün, F. & Blumberg, B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signalling. Endocrinology 147 (Suppl. 6), S50–S55 (2006).

    PubMed  Google Scholar 

  98. 98

    Golub, M. & Doherty, J. Triphenyltin as a potential human endocrine disruptor. J. Toxicol. Environ. Health B. Crit. Rev. 7, 281–295 (2004).

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

M. I. Goran, S. G. Bouret, B. Kayser, R. W. Walker and B. Blumberg researched the data for the article. All authors contributed to writing the manuscript, provided substantial contributions to discussions of its content, and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Michael I. Goran.

Ethics declarations

Competing interests

Bruce Blumberg declares that he is a named inventor on the following US patents: 5,861,274 Nucleic acids encoding peroxisome proliferator-activated receptor; 6,200,802 Human peroxisome proliferator activated receptor gamma: compositions and methods; 6,815,168 Human peroxisome proliferator activated receptor gamma: compositions and methods; and 7,250,273 9 Human peroxisome proliferator activated receptor gamma: compositions and methods.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Goran, M., Dumke, K., Bouret, S. et al. The obesogenic effect of high fructose exposure during early development. Nat Rev Endocrinol 9, 494–500 (2013). https://doi.org/10.1038/nrendo.2013.108

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing