Research Description
Ceramides are fat molecules that accumulate in individuals with obesity, diabetes and heart disease. Recent research findings have shown that blocking ceramide synthesis production in fat/adipose tissue improves adipose tissue role in producing appropriate hormones for metabolism and endocrine functions in the body. This project proposes two innovative aims to investigate the strength of these findings in mouse models. Aim 1 is to determine the effect of ceramide biosynthesis pathway effector molecular protein, fibroblast growth factor (Fgf)13, on modulating adipose metabolism and thermogenesis. The hypothesis is that by reducing the amounts of FGF13 proteins regulated by ceramide biosynthesis pathway will improve adipose tissue metabolism. An anticipated outcome would be uncovering new therapeutic approaches for obesity and associated diseases, such as diabetes and heart diseases. Aim 2 is to define the molecular mechanisms via which ?-adrenergic agonist such as catecholamines inhibit ceramide synthesis in adipose tissue and how ceramide biosynthesis pathway modulates Fgf13 expression. The hypothesis is that firstly, catecholamines inhibit ceramide synthesis by regulating either expression or activity of the enzymes essential for ceramide synthesis. Secondly, ceramide biosynthesis pathway modulates thermogenesis by modulating Fgf13 expression. An anticipated outcome is revealing a new beta-adrenergic-ceramide biosynthesis pathway-FGF13 regulatory axis essential for modulating thermogenesis.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?My work focuses on understanding how ectopic lipid accumulation triggers the development of type 2 diabetes. We focus on one particular type of lipid molecule called ceramides that we have found in our earlier studies to be highly toxic towards inhibiting insulin ability to safely clear and store glucose. From the therapeutic standpoint, we and others have found that pharmacological and genetic interventions, that reduces ceramide accumulation improves insulin action and reduce blood glucose levels, suggesting that safely targeting ceramide biosynthesis can offer a means to prevent the development of diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Better understanding of how toxic lipid metabolite ceramide impair adipose tissue function, will lead to the identification of new targets that could be therapeutically exploited to improve insulin action. To this end we have identified a protein, that is regulated by ceramides in adipose tissue and cause the development of obesity and diabetes. With better understanding of how this protein modulate adipose tissue function, we might be able to design drugs to target this protein as a means to improve adipocyte function and prevent the development of obesity and associated diseases, such as diabetes and heart diseases.
Why important for you, personally, to become involved in diabetes research? What role will this award play?My aim has always been to be a national expert in molecular and genetic underpinnings of metabolic diseases focused on translating scientific findings to advance the treatment of diabetes. Through receipt of this award, both I and my research have the potential and quality necessary to successfully advance diabetes research and my trajectory towards independence in my intended career in diabetes research would be ensured.
In what direction do you see the future of diabetes research going?By studying the newly identified protein that is regulated by ceramides and how it improves adipose tissue function, we hope we can design new drugs that prevents the development of obesity and associated diseases, such as diabetes and heart diseases.