Critical Windows in the Developmental Programming of Physical Exercise by Nutrition

Physical activity (PA) is critical for maintenance of optimal health throughout life. Moreover, PA is being increasingly prescribed for the treatment of many metabolic and endocrine diseases, including obesity and type 2 diabetes. While there is extensive research on the influence of lifestyle and the physical and social environment on voluntary PA, it is emerging from epidemiological studies, and supported by our own experimental data from mice, that the nutritional environment of the developing organism also can program voluntary PA in childhood and adulthood. The overall goals of the studies within this plan are to use the mouse model to: define the nutritional perturbations (over- and under-nutrition) and critical windows of development (pre- vs. postnatal) that alter PA in adulthood; define the type of activity that is altered; and elucidate the physiological basis for the observed changes. The studies are guided by the concept that voluntary PA is a function of the capacity and the motivation for PA. These parameters are regulated by peripheral (skeletal muscle and cardio-respiratory) and central (brain) mechanisms that are known to be vulnerable to programming by the early life environment.  This information is critical for the identification of populations who are at risk for reduced PA, and for the design of individualized interventions that are more likely to be effective in producing positive outcomes.

Research Faculty: Marta Fiorotto

Modifying Plant Transport Processes for Enhanced Nutritional Quality of Plant Foods

The long-term objectives of this research are to contribute to the development of nutritionally enhanced plant foods and to assess the potential role of plant-derived microRNAs in human health.

We will work with plants that are tractable molecular genetic systems (Arabidopsis, Medicago, and soybean) where we can perform gene discovery or genetic transformation quickly. Genome-wide association analysis will be employed to identify genomic loci associated with altered nutritional traits. We will identify the genes in plants that synthesize oxalate and calcium oxalate, using the model legume Medicago truncatula, and this information will be used to design strategies to manipulate oxalate content in important food plants (such as soybean) for the purpose of improving nutritional quality.

Experiments will also be conducted to determine whether food-associated plant microRNAs are present and functional in sera and tissues, and to establish the relationship between dietary microRNA intake and metabolic changes.

We will gain fundamental insights into the genetic foundations for variations in responses to dietary lycopene and to understand how the food component lycopene may be acting to promote health and prevent chronic diseases.

Research Faculty:  Kendal D. Hirschi / Paul Nakata / Nancy E. Moran

The Pathophysiology of Lactation in Obesity

The goal of this project is to understand the genetic, hormonal, and psychological factors that regulate mammary gland function in lactating mothers and in the maternal-infant interactions.  It is well known that obese women struggle to lactate.  In Objective 1 we will determine the role of postpartum plasma progesterone in lactation failure in obese women.  In Objective 2 we will explore factors that might affect mammary gland development and function in lean and obese mice. These factors include the use of genetically modified mouse models and pharmacological approaches to determine the roles of inflammation, inflammatory cells, and markers of inflammation as well as mineralocorticoids. In addition, we will determine the relationship of maternal oxytocin response and maternal-infant sensitivity, breastfeeding duration and efficacy, and maternal brain response using functional magnetic resonance imaging in obese and non-obese lactating women (Objective 3). The successful completion of these objectives will provide us collectively with new and important insights into the impact of obesity on the pathophysiology of  lactation failure by examining many aspects of mammary physiology from secretory activation and function (the role of progesterone and inflammation), and maternal-infant interaction. From these investigations, we anticipate the development of new therapeutic interventions that will positively impact both maternal and infant nutrition and health outcomes by increasing the success of breastfeeding in women who are overweight or obese.

Research Faculty: Morey Haymond / Daryll Hadsell