Our research is focused on obesity and understanding how immune cells in fat tissue contribute to inflammation and insulin resistance. We are attempting to find out how and why oxidative stress in fat can lead to activation of these immune cells, in particular, which proteins are necessary for these immune cells to be activated in this fashion. Our group has already identified some potential proteins necessary for this process. Like many other labs, we are using genetically engineered mice that are lacking these proteins of interest in order to truly see if they are required for the negative effects stated previously. We would like to put these mice on a diet similar to what humans would become obese from. We will see whether the mice lacking these certain proteins will be protected from developing inflammation and insulin resistance. We will also treat mice with an inhibitor of a protein responsible for inflammation to hopefully improve insulin sensitivity. We believe that our work will lead to the discovery and testing of new drug targets that may one day be exploited in order to prevent the onset of insulin resistance and other comorbidities of obesity. One of our proteins of interest is already has drugs which disable it that have reached clinical trials for treating rheumatoid arthritis. Our work will test new uses for these drugs in combating insulin resistance and provide the groundwork for establishing new drugs to counter the morbidity of obesity.

Public Health Relevance

This study will test whether spleen tyrosine kinase (Syk) inhibition will ameliorate adipose tissue inflammation and insulin resistance. This project will provide new insight into the connection between cellular metabolism and inflammatory function in the context of oxidized phospholipid-driven chronic inflammation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DK108553-01A1
Application #
9122610
Study Section
Special Emphasis Panel (ZDK1-GRB-R (J1)L)
Program Officer
Castle, Arthur
Project Start
2016-07-01
Project End
2018-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$30,812
Indirect Cost
Name
University of Virginia
Department
Pharmacology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Kerur, Nagaraj; Fukuda, Shinichi; Banerjee, Daipayan et al. (2018) cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. Nat Med 24:50-61
Serbulea, Vlad; Upchurch, Clint M; Ahern, Katelyn W et al. (2018) Macrophages sensing oxidized DAMPs reprogram their metabolism to support redox homeostasis and inflammation through a TLR2-Syk-ceramide dependent mechanism. Mol Metab 7:23-34
Serbulea, Vlad; Upchurch, Clint M; Schappe, Michael S et al. (2018) Macrophage phenotype and bioenergetics are controlled by oxidized phospholipids identified in lean and obese adipose tissue. Proc Natl Acad Sci U S A 115:E6254-E6263
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