High-fructose diet in pregnancy leads to fetal programming of hypertension, insulin resistance, and obesity in adult offspring

Saad, Antonio F.; Dickerson, J W; Kechichian, Talar; Yin, Huaizhi; Gamble, Phyllis; Salazar, Ashley; Patrikeev, Igor; Motamedi, Massoud; Saade, George R.; Costantine, Maged M.

doi:10.1016/j.ajog.2016.03.038

Cited by 76 publications

(66 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, limited data are available at present on the effects of maternal fructose consumption on the BP of adult offspring. Studies listed in Table 1 indicate that consumption of HF alone or as a part of diet by rodent mothers induces programmed hypertension in adult offspring [26,27,28,29,30,31,32,33]. We found that adult offspring of mothers exposed to 60% HF diet during pregnancy and lactation developed hypertension [26], which is consistent with the results of earlier studies involving fructose-fed adult rats [16,19].…”

Section: Effect Of Maternal Fructose Consumption On Programmed Hypsupporting

confidence: 90%

Maternal Fructose Intake Affects Transcriptome Changes and Programmed Hypertension in Offspring in Later Life

2016

View full text Add to dashboard Cite

Hypertension originates from early-life insults by so-called “developmental origins of health and disease” (DOHaD). Studies performed in the previous few decades indicate that fructose consumption is associated with an increase in hypertension rate. It is emerging field that tends to unfold the nutrient–gene interactions of maternal high-fructose (HF) intake on the offspring which links renal programming to programmed hypertension. Reprogramming interventions counteract disturbed nutrient–gene interactions induced by maternal HF intake and exert protective effects against developmentally programmed hypertension. Here, we review the key themes on the effect of maternal HF consumption on renal transcriptome changes and programmed hypertension. We have particularly focused on the following areas: metabolic effects of fructose on hypertension and kidney disease; effects of maternal HF consumption on hypertension development in adult offspring; effects of maternal HF consumption on renal transcriptome changes; and application of reprogramming interventions to prevent maternal HF consumption-induced programmed hypertension in animal models. Provision of personalized nutrition is still a faraway goal. Therefore, there is an urgent need to understand early-life nutrient–gene interactions and to develop effective reprogramming strategies for treating hypertension and other HF consumption-related diseases.

show abstract

Section: Effect Of Maternal Fructose Consumption On Programmed Hypsupporting

confidence: 90%

Maternal Fructose Intake Affects Transcriptome Changes and Programmed Hypertension in Offspring in Later Life

2016

View full text Add to dashboard Cite

show abstract

“…Once animal studies reveal the detailed morphological changes, molecular signaling pathways and epigenetic alterations, clinical applications using advanced imaging technologies, peripheral miRNA determinations, metabolomic and proteomic approaches 92–95 can be designed for early diagnosis, monitoring prognosis after interventions, and the development of effective treatments. High glucose is the major teratogen in diabetic pregnancy 75, 96 . Future studies may focus on the downstream molecular targets of glucose and recapitulate the key findings of animal studies in possible vascular tissues such as blood vessels in the placenta.…”

Section: Commentmentioning

confidence: 99%

Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis

Xue

Yang

Reece

2017

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

Background Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Experimental evidence has implied that pregnant women with T2DM and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study has revealed that maternal T2DM induces structural heart defects in their offspring. Objective The present study aims to determine whether maternal T2DM induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. Study design The T2DM embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet (HFD) for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), insulin-like growth factor 1 (IGF1), desmin (DES), and adrenomedullin (ADM). Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor (CTGF), osteopontin (OPN), and Galectin 3 (GAL3) genes. Cell apoptosis also was measured in the developing heart. Results The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic (ND) group. Maternal diabetes significantly increased β-MHC, ANP, IGF1 and DES expression, but decreased expression of ADM. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, GAL3, was induced by maternal diabetes. Furthermore, maternal T2DM activated the pro-apoptotic c-Jun-N-terminal kinase (JNK1/2) stress signaling and triggered cell apoptosis by increasing the number of TUNEL positive cells (10.4 ± 2.2% of the T2DM group vs. 3.8 ± 0.7% of the ND group, P < 0.05). Conclusions Maternal T2DM induces cardiac hypertrophy in embryonic hearts. Adverse cardiac remodeling, including elevated collagen synthesis, suppressed fibronectin synthesis, profibrosis and apoptosis, is implicated as the etiology of cardiac hypertrophy.

show abstract

“…In our study, women with gHTN had five metabolic pathways that were significantly enriched with four involving amino acid metabolism or catabolism and one involving fructose metabolism. Diets high in fructose consumption have been linked with cardiometabolic disease [59], and recent animal studies have shown an association between maternal fructose consumption and the incidence of hypertension in their offspring [60].…”

Section: Discussionmentioning

confidence: 99%

Early Pregnancy Serum Metabolite Profiles Associated with Hypertensive Disorders of Pregnancy in African American Women: A Pilot Study

Ferranti

Frediani

Mitchell

et al. 2020

Journal of Pregnancy

View full text Add to dashboard Cite

Hypertensive disorders of pregnancy (HDP) are the most common cardiometabolic complications of pregnancy, affecting nearly 10% of US pregnancies and contributing substantially to maternal and infant morbidity and mortality. In the US, women of African American race are at increased risk for HDP. Early biomarkers that reliably identify women at risk for HDP remain elusive, yet are essential for the early identification and targeting of interventions to improve maternal and infant outcomes. We employed high-resolution metabolomics (HRM) to identify metabolites and metabolic pathways that were altered in early (8-14 weeks) gestation serum samples of pregnant African American women who developed HDP after 20 weeks’ gestation (n=20)—either preeclampsia (PE; n=11) or gestational hypertension (gHTN; n=9)—compared to those who delivered full term without complications (n=80). We found four metabolic pathways that were significantly (p<0.05) altered in women who developed PE and five pathways that were significantly (p<0.05) altered in women who developed gHTN compared to women who delivered full term without complications. We also found that four specific metabolites (p<0.05) were distinctly upregulated (retinoate, kynurenine) or downregulated (SN-glycero-3-phosphocholine, 2′4′-dihydroxyacetophenone) in women who developed PE compared to gHTN. These findings support that there are systemic metabolic disruptions that are detectable in early pregnancy (8-14 weeks of gestation) among pregnant African American women who develop PE and gHTN. Furthermore, the early pregnancy metabolic disruptions associated with PE and gHTN are distinct, implying they are unique entities rather than conditions along a spectrum of the same disease process despite the common clinical feature of high blood pressure.

show abstract

High-fructose diet in pregnancy leads to fetal programming of hypertension, insulin resistance, and obesity in adult offspring

Cited by 76 publications

References 51 publications

Maternal Fructose Intake Affects Transcriptome Changes and Programmed Hypertension in Offspring in Later Life

Maternal Fructose Intake Affects Transcriptome Changes and Programmed Hypertension in Offspring in Later Life

Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis

Early Pregnancy Serum Metabolite Profiles Associated with Hypertensive Disorders of Pregnancy in African American Women: A Pilot Study

Contact Info

Product

Resources

About