Maternal Exposure to High Fructose and Offspring Health

Jia G, Hill MA and Sowers JR.

Hypertension 2019; 74:499-501. DOI: 10.1161/HYPERTENSIONAHA.119.13017

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  • Seong, et al. investigated whether maternal exposure to high fructose induces hypertension together with RAAS activation, renal tissue oxidative stress, inflammation, and tissue fibrosis in successive multiple generations. 
  • Specifically, maternal exposure to high fructose significantly increased blood pressure in the first and second-generation offspring along with increased serum Ren, angiotensin II, and aldosterone levels, as well as abnormal mRNA expression for Ren1, angiotensinogen, Ace, Ace2, Agtr1, Agtr2, and Mas. Furthermore, maternal exposure also induced abnormal renal mRNA expression of sodium transporters Slc9a3, Slc12a1, Slc12a3, and Scnn1b in multiple generations of the adult offspring.

Summary of Comments

  • It is increasingly recognized that high dietary fructose intake, in
    the form of high-fructose corn syrup, is a major contributor to the increasing
    prevalence of obesity and has adverse effect on health outcomes. Recent reports
    suggest that consumption of high-fructose diets by mothers during pregnancy and
    lactation induces renal programming leading to hypertension in adult offspring.
  • The mechanisms by which high maternal fructose consumption leads to
    programmed hypertension include excessive oxidative stress, activation of the
    renin-angiotensinaldosterone system (RAAS), increased sympathetic nerve
    activity, dysregulation of nutrient-sensing signals, increased uric acid,
    impaired endothelium-dependent relaxation, abnormal gut microbiota composition
    which are abnormalities impacted by sexual dimorphism.
  • Activation of nutrient-sensing signaling pathways, such as adenosine
    monophosphate-activated protein kinase and peroxisome proliferator-activated
    receptors, increases in uric acid and oxidative stress, and attenuation of the
    nitric oxide pathway, are also involved in RAAS activation-related hypertension
    of developmental origin (in adult offspring) induced by maternal and postnatal
    high-fructose intake.
  • In concert with RAAS activation and resultant programmed hypertension,
    maternal high fructose consumption also induces abnormal expression of renal
    sodium transporters, excessive oxidative stress, inflammation, and renal
    fibrosis in adult offspring.
  • The data from the present study highlight the role for maternal high
    dietary fructose intake in increasing the risk of development of hypertension
    in multigenerational offspring through activation of RAAS, increased
    vasocontractile peptides, renal sodium transporters, oxidative stress, and
  • However, clarification is needed regarding the following:
    • The adverse effects of fructose feeding appear
      to depend on both the amount and duration of fructose consumption. Provision of
      a strong rationale for the maternal 20% high-fructose intake and the 8-month
      determination of blood pressure values in the offspring would have been
    • The current study does not identify
      fundamental sex-specific differences in RAAS activation, sodium transporters,
      oxidative stress factors, and inflammation induced by maternal high-fructose
      intake in the multigenerational offspring.


  • The present study is consistent with and extends previous studies in which maternal and post-weaning high-fructose diets induced hypertension of developmental origin.
  • The results show an important role of maternal exposure to high fructose during pregnancy and lactation in development of multigenerational RAAS activation and associated hypertension. Indeed, reductions in maternal fructose consumption may be a novel recommendation and therapeutic strategy for preventing multigenerational hypertension and associated cardiovascular and renal diseases.
  • Additional studies, including in humans, are warranted to more definitively understand the relative role of high fructose consumption in maternal diet-induced cardio-renal metabolic abnormalities and vascular stiffness in conjunction with hypertension.