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Date of Award

Summer 8-15-2016

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Cell Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type



Intake of fructose in the form of sucrose and high-fructose corn syrup has risen dramatically over the past few decades and been implicated in development of metabolic syndrome, which includes obesity, dyslipidemia, hypertension and impaired glucose homeostasis. Unlike glucose, fructose metabolism preferentially drives the production of triglycerides and uric acid. Although uric acid is a normal by product of purine metabolism, fructose induced hyperuricemia has been linked to insulin resistance, elevated serum triglycerides and increased risk of type 2 diabetes by leading to cellular inflammation and oxidative damage. There is a growing incidence of metabolic diseases in reproductive age women and is associated with increased obstetric complications such as preeclampsia, gestational diabetes, and intrauterine growth restriction which predisposes the offspring to obesity and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring and is likely mediated by impairing function of the placenta, the transitory organ that mediates exchange of nutrients and wastes between the mother and fetus. However, the mechanism by which consumption of a high-fructose diet impairs placental function and the in utero milieu is unknown. Here, we assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome or hyperuricemia and determined the association between maternal serum fructose and placental uric acid levels in humans. We found that in mice excess maternal fructose consumption leads to placental inefficiency, fetal growth restriction as well as elevated fetal serum glucose and triglycerides. In the placenta, the fructose metabolic pathway leading to de novo production of uric acid was upregulated leading to significant accumulation of uric acid. Treatment of high-fructose-fed mothers with allopurinol to inhibit uric production reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Moreover, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a uric acid-dependent mechanism, and similar effects may occur in humans. The negative consequences of fructose consumption on metabolic health are still debated. We found that while acute exposure to fructose increases insulin secretion in isolated mouse islets and may be beneficial to glucose homeostasis, chronic consumption leads to impaired glucose tolerance. Importantly, we report that fructose has detrimental effects on pancreatic islet function as fructose-fed mice exhibited defects in both insulin and glucagon secretion contributing to hyperglycemia. Fructose consumption in humans may precipitate similar defects before the onset of full-blown metabolic syndrome. Thus consumption of fructose in non-naturally occurring forms should be limited, particularly during pregnancy.


English (en)

Chair and Committee

Kelle H. Moley

Committee Members

Thomas J. Baranski, Sarah K. England, D. Michael Nelson, Maria S. Remedi, Fumihiko Urano


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