More than 68 million people in the United States are insulin resistant and the problem is becoming particularly acute in young adults. Excessive fructose intake induces insulin resistance and one-fourth of all the children in the United States have fructose intakes that puts them at risk in this regard. The biochemical and molecular roots of insulin resistance and other components of the metabolic syndrome are established as a consequence of in utero environment and fully manifested in response to postnatal diet. Supportive evidence from the literature indicates that insulin resistance in offspring is induced by maternal under- nutrition as well as maternal over-nutrition and is modulated by postnatal diet. Available information indicates that maternal nutrition causes lasting changes in expression of insulin responsive genes in liver of the offspring as predisposing factors for insulin resistance. Understanding the impact of dietary habits during pregnancy, and link to foods consumed in postnatal life, is critical to unraveling the impact of fetal programming in relation to the current insulin-resistance and diabetes epidemic. Comprehensive studies do not exist in either laboratory animals or human subjects that explore the links between fetal programming, postnatal fructose consumption, and insulin resistance. Likewise studies do not exist to determine the role of fructose consumption during pregnancy on insulin resistance in the offspring. The fundamental objective of this proposal is to determine links that exist between fetal programming and fructose-induced insulin resistance and the role of maternal fructose consumption in this process. Our preliminary data indicates that insulin resistance is rapidly inducible in rats fed high fructose diets. Our central hypothesis is that high fructose diets lead to fetal programming that sensitizes offspring to fructose-induced insulin resistance in later life. The proposed studies address the following two specific aims 1) to determine sensitivity to fructose- induced insulin resistance in an established model of fetal programming and 2) to determine the effects of maternal fructose consumption on birth weight, postnatal growth, and insulin resistance in the offspring. This research is relevent to public health in that it will explore the impact of a current food choice in the United States towards increased fructose consumption and examines the interaction between fructose consumption during pregnancy and subsequent insulin resistance in the offspring. [unreadable] [unreadable] [unreadable]