Grove, Kevin L., PhD
Developmental programming of leptin signaling in arcuate neuropeptide Y neurons
General Research Subject: Obesity
Focus: Integrated Physiology, Integrated Physiology\Regulation of Food Intake, Obesity, Obesity\Animal Models, Pediatrics, Pediatrics\Obesity
Type of Grant: Mentor Based Minority Postdoctoral Fellowship
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
The incidence of preventable diseases such as obesity among children has markedly increased during the last 20 years. This emerging epidemic of childhood obesity is partially due to the availability of highly palatable and calorically rich diets. Obese children and adolescents are considered at high risk for the development of type 2 diabetes and heart disease. Currently, there is little information regarding how overnutrition at a young age may alter the function of regulatory systems in the brain that control feeding behavior.
The proposed studies will use a transgenic rodent model to investigate how leptin, a hormone produced by fat tissue, regulates brain pathways that modulate food intake during important periods of development. The second objective of this proposal will focus on the impact of early overnutrition on the development of abnormalities in the leptin signaling. It is hypothesized that leptin regulation of feeding circuits in the brain may have differential functions during development than it does in adults. It is expected that overnutrition during development will disrupt the mechanisms of leptin regulation in the brain, increasing the animals' susceptibility to metabolic diseases such as diabetes. These studies will provide important insights about the role of leptin in early nutritional reprogramming. These insights may help further our understanding of childhood obesity and its long-term impact on the development of diabetes.
Mentor: Kevin Grove, PhD Postdoctoral Fellow: Arian Ferney Baquero Gonzalez, PhD
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Our research project is focused on how over nutrition during important periods of development may impact the development of brain regions involved in the regulation of food intake, glucose homeostasis and insulin secretion from the pancreas. These developmental abnormalities in turn increase the risk for obesity, type 2 diabetes, and heart disease later on in life. Identifying these critical periods of development and the environmental factors that alter the development of the brain provide important insight into how to prevent metabolic diseases (such as diabetes) as well as helping understand the pathogenesis of the disease, which will also be important for developing novel therapeutics.
If a person with diabetes were to ask you how your project will help them in the future,
how would you respond?
The key outcomes from our study, while focused on the development of the brain and on the prevention of diabetes, still has significant relevance for the treatment of complications in people that already have diabetes. These studies will help identify abnormalities in brain circuits that are known to be involved in the regulation of glucose production and clearance. Thus, we feel that these studies may help identify novel targets for the treatment of diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I personally have gotten involved in diabetes risk because my family has demonstrated a risk for the development of this disease. Through my years of research in this area we feel that we have identified critical periods of development that can be targeted as periods of intervention that would greatly reduced the risk of future development of diabetes. For example, we know that poor maternal nutrition and metabolic health leads to a dramatic increase in the risk of children developing diabetes. We feel that improving the diet and health of women specifically during this period can have a long-term impact on overall health of the children. More so that trying to treat the disease after it develops.
In what direction do you see the future of diabetes research going?
The current proposed studies uses rodent models to help identify molecular and cellular abnormalities caused by over nutrition during the postnatal period. The studies in the rodents are important and provide a model in which we can perform extensive model manipulations and use the powerful molecular genetics that are available in this species. However, there are some significant differences in the relative timing of development of the brain between rodents and humans. Furthermore, the brain circuity in the human that controls body weight and glucose homeostasis is more complex than in the rodent. Therefore, future studies will utilize a novel and powerful nonhuman primate model that we have developed to help translate this research into the clinic. We already have a proven track record of this advanced translational research in other areas of obesity/diabetes research. Including the development of novel therapeutic targets.
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