News & Research

Research Description

When rats and mice that are genetically susceptible to obesity consume a high-fat diet, the result is injury to neurons in the hypothalamus, as well as reactive gliosis -- the brain's protective response to injury. The specific area of the hypothalamus damaged by high-fat feeding is critical to regulating body weight and glucose metabolism. The investigators who obtained these results in animals also recently used magnetic resonance imaging (MRI) to provide the first evidence of similar hypothalamic damage in obese humans.

The objective of the proposed study is to test whether damage (gliosis) in the human hypothalamus is related to insulin resistance. In addition, the investigators will conduct a pilot study that uses functional MRI to examine whether neural activity in the hypothalamus in response to oral glucose is impaired when MRI examinations reveal hypothalamic gliosis. This proposal will thus use findings from animal studies to better understand the role of the brain in developing insulin resistance and, potentially, type 2 diabetes (T2D) in obese humans.

The anticipated results will lay the foundation for future clinical trials using longitudinal designs to test whether hypothalamic gliosis precedes, predicts, or is otherwise related to the onset of T2D. The proposed work addresses the question of whether damage to the human hypothalamus contributes to obesity, insulin resistance, and diabetes. It may also identify an early warning sign of T2D that could be applied in clinical care or in research to design and test the effectiveness of interventions to prevent T2D.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?

When rats and mice that are genetically susceptible to obesity consume a high-fat diet, the result is injury to neurons in the hypothalamus, as well as reactive gliosis -- the brain's protective response to injury. The specific area of the hypothalamus damaged by high-fat feeding is critical to regulating body weight and glucose metabolism. The investigators who obtained these results in animals also recently used magnetic resonance imaging (MRI) to provide the first evidence of similar hypothalamic damage in obese humans.

The objective of the proposed study is to test whether damage (gliosis) in the human hypothalamus is related to insulin resistance. In addition, the investigators will conduct a pilot study that uses functional MRI to examine whether neural activity in the hypothalamus in response to oral glucose is impaired when MRI examinations reveal hypothalamic gliosis. This proposal will thus use findings from animal studies to better understand the role of the brain in developing insulin resistance and, potentially, type 2 diabetes (T2D) in obese humans. The anticipated results will lay the foundation for future clinical trials using longitudinal designs to test whether hypothalamic gliosis precedes, predicts, or is otherwise related to the onset of T2D.

The proposed work addresses the question of whether damage to the human hypothalamus contributes to obesity, insulin resistance, and diabetes. It may also identify an early warning sign of T2D that could be applied in clinical care or in research to design and test the effectiveness of interventions to prevent T2D.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

We are trying to identify early warning signs of type 2 diabetes and learn how to better prevent type 2 diabetes.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?

I take care of many patients with diabetes in my clinic. It is important to me to help people better understand ways in which they can prevent diabetes. This research will provide new information about how the brain changes in obesity and diabetes. In particular, we hope to discover how diet changes may prevent diabetes.

In what direction do you see the future of diabetes research going?

In the future, I hope that we can recommend diet changes that will help prevent diabetes at the level of the brain.