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Brenner, Michael, MD

Brigham and Women's Hospital, Boston, Massachusetts

Project Title:

Identify Lipid Antigens in Fat that Activate Lipid Sensing iNKT Cells and Protect Against Diet Induced Obesity and Insulin Resistance

Grant Number:

7-12-IN-07

Type of Grant:

Innovation

General Research Subject:

Type 2 Diabetes

Project Start Date:

Jul 1, 2012

Project End Date:

Jun 30, 2014

Focus:

Immunology, Obesity, Obesity\Animal Models, Obesity\Pathogenesis

Research Description



Inflammation plays a key role in obesity and diabetes. We found a special type of white blood cell, the called "NKT cells" are present in very large numbers in fat tissue in people and in experimental animals. These special white blood cells control rather than aggravate inflammation in fat tissue. Their numbers drop and their ability to control inflammation is lost when animals are fed a high fat diet and become obese. However, returning these cells to animals corrects the weight gain and reverses the diabetic state. In the application, we propose to identify the antigens that stimulate these beneficial white blood cells. But, the antigens are different from those known to stimulate most white blood cells, since they are actually fats themselves. We will determine which fat-type antigens activate the beneficial white blood cells and then test if administering them to obese animals can correct the weight gain and the diabetic state. These studies will provide new insights into the role of fats as activators of white blood cells and immune modulators that are relevant to regulating inflammation in obesity and Type II Diabetes.

Research Profile



What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
The project focuses on the role of inflammation in obesity and diabetes. We found a special type of white blood cell, called NKT cells that are present in very large numbers in fat tissue in people and in experimental animals. These special white blood cells control rather than aggravate inflammation in fat tissue. Their numbers drop and their ability to control inflammation is lost when animals are fed a high fat diet and become obese. However, returning these cells to animals corrects the weight gain and reverses the diabetic state. In the application, we propose to identify the antigens that stimulate these beneficial white blood cells. But, the antigens are different from those known to stimulate most white blood cells, since they are actually special lipids or fats themselves. We will determine which fat-type antigens activate the beneficial white blood cells and then test if administering them to obese animals can correct the weight gain and the diabetic state. These studies will provide new insights into the role of fats as activators of white blood cells and immune modulators that are relevant to regulating inflammation in obesity and Type II Diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
The fat (lipid) antigens that we hope to identify as described above, could potentially be given to people as a new type of drug for type II diabetes. Our studies have the potential to identify a whole new way of modifying the type of inflammation that is specifically found in obesity associated diabetes.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
My research career has focused on the basic biology of inflammation. The ultimate goal of such basic research is to treat human disease. I realized that some of my basic research on the role of lipids in inflammation may be especially relevant for obesity and type II diabetes. But I have not worked in this particular area before. So, this pilot award is making it possible for me to initiate diabetes research for the first time in my lab. I know how important diabetes is as a disease and I am very excited and eager to apply my area of special expertise as a new investigator in diabetes. If the work we carry out supported by this pilot grant is successful, I will then move forward to continue working on diabetes as I seek further funding to carry the project forward.

In what direction do you see the future of diabetes research going?
There are many relevant aspects to diabetes, but the role of inflammation is one of the most important aspects that has relevance to prevention and treatment. The role of inflammation has been known for a long time is leading to the destruction of islets in Type I diabetes, but the role of inflammation in obesity and type II diabetes is now increasingly being appreciated as well. In this case, the inflammation is in the fat tissue rather than the pancreas. This is a new and likely very important concept that may bring special opportunities for preventing and treating type II diabetes.