Research Description
Obesity and diabetes are among the most prevalent and growing health issues in the United States and around the world. These diseases are associated with other complications, such as cardiovascular disease, osteoarthritis and certain cancers, which put enormous financial burdens on individuals, families and countries. Significant efforts thus have been made to alleviate the outbreak of this epidemic, but so far limited success has been achieved. One important finding that can help us better address this problem is that fat tissue is not just a place to keep excess calories but is in fact a central organ that controls systemic energy and nutrient metabolism. The functional failure of fat tissue is a critical step that precede the onset of Type 2 diabetes and other metabolic disorders. Therefore, there has been interest in finding approaches that can ‘reprogram’ fat tissues from an unhealthy state to a healthy state. However, we are held back by a lack of knowledge about the factors and pathways that regulate the states of fat cells. Dr. Roh’s group discovered that fat cells acquire maladaptive functional characteristics resembling a muscle-like cell type directed by a gene called SRF during obesity. The overall goal of this proposal is to understand this pathological change and apply this finding to enhance fat tissue function and improve nutrient metabolism in the body. These studies will enable new therapeutic approaches for metabolic diseases like obesity and 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?Adipose tissue is a key metabolic organ maintaining energy homeostasis capable of scaling up and down in response to nutrient availability and is directly affected by obesity. Prolonged obesity causes adipose tissue dysfunction, leading to systemic metabolic defects, including peripheral lipid deposition and insulin resistance. This is a critical step preceding the onset of type 2 diabetes and other metabolic disorders. During this pathological process, several biological pathways involved in inflammation, fibrosis and hypoxia are known to play an important role in the actions of a range of cell types including immune cells and endothelial cells in the adipose tissue. However, we lack understanding of the mechanisms by which adipocytes themselves become dysfunctional during obesity. Our preliminary data using adipocyte-targeted molecular analysis demonstrated that obesity causes adipocytes to go through ‘aberrant cellular reprogramming’, characterized by induction of myofibroblast-like molecular and cellular phenotypes. This project will determine the molecular mechanisms that drive such pathological changes in adipocytes during obesity. Completion of these studies could lead to the development of new preventive and therapeutic strategies for type 2 diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Obesity and type 2 diabetes are among the most prevalent and growing health issues in the United States and around the world. As they are associated with other complications, such as cardiovascular disease, liver disease and certain cancers, obesity and type 2 diabetes-associated medical costs are a huge economic burden. It is now a priority to develop safe and effective therapeutic approaches for the treatment of these disorders. The specific problem is that despite the critical role of adipose tissue in nutrient metabolism, there are surprisingly few clinically-approved, safe and effective therapeutic approaches that specifically target adipocytes. This proposal represents a new avenue of adipose biology, with the potential to lead to novel therapeutic interventions for the treatment of obesity, diabetes and associated metabolic disorders.
Why important for you, personally, to become involved in diabetes research? What role will this award play?Energy homeostasis is a fundamental biological process essential for all living creatures. Since diabetes results from defects in such an essential biological process, I believe that diabetes research holds a key not only to the treatment of metabolic diseases but also to understanding of broad spectrum of human disease and health. This award will play a critical role in supporting me to tackle unexplored areas of adipose biology, develop my research topics and to establish myself as an independent investigator.
In what direction do you see the future of diabetes research going?Diabetes is a complicated disease; each patient responds differently to treatments. We now see the genomics revolution continuing to develop quickly, and I believe diabetes treatment will be based on the genomics and epigenomics of the individual patient.