Ma, Ke , MD, PhD
The clock gene, Brain and Muscle Arnt-like 1, suppresses brown adipocyte cell fate via TGFb/BMP signaling pathways
General Research Subject: Obesity
Focus: Adipocytes, Obesity\Animal Models, Signal Transduction (Non-Insulin Action)\Transcriptional Regulation
Type of Grant: Basic Science
Project Start Date: January 1, 2013
Project End Date: December 31, 2015
Diabetes Type: Type 2 diabetes
Brown fat is a tissue type specializing in burning energy to generate heat for maintenance of body temperature. This unique property can thus be utilized to combat obesity and its associated diseases. The biological clock system can control important pathways that regulate metabolic processes and one of the genes involved in generating the clock rhythm, Bmal1 was shown to prevent fat formation in mice. But whether it affects brown fat development has not been studied. Therefore, this proposal is aimed to investigate the hypothesis that Bmal1 may suppress the formation of brown fat through its control of signals that prevents brown fat development. Specific experiments are designed to prove this first in adipose stem cells that are capable of becoming brown adipocytes, identify its molecular targets in developmental signals that control brown fact formation and test its influence on brown fat using mice lacking Bmal1 in precursor cells that becomes brown fat in adult life. These studies will help to identify new mechanisms controlling the formation of brown fat, which may be targeted for interventions to treat obesity.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?
Our project studies the effect of the biological clock network on the formation of brown fat, a specialized organ for dissipating heat to maintain body temperature. Due to its high demand for oxidative metabolism, augmenting the activity or the amount of brown fat to increase energy expenditure could become an effective therapeutic strategy to prevent obesity. Accumulating evidence indicates that alterations or disruption of the biological clock system could lead to obesity and our study suggests that the clock regulation of the maturation of brown fat cells or its metabolic activity is one potential underlying mechanism mediating these effects. Therefore, understanding of the precise molecular pathways influencing brown fat formation and activation that are under the clock control may lead to discoveries of targeted strategies to prevent development of obesity, through either preservation or modulation of the clock network.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Obesity impairs the body's sensitivity to utilize glucose and is a significant factor contributing to development of type II diabetes. Our project will investigate how the body's natural clock system influences energy consumption through its control of the maturation of brown fat. Therefore, our research may help to find specific ways to manipulate the biological clock to combat obesity and thus to prevent the development of diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
Obesity and the resultant type II diabetes has become an epidemic in the modern society and our life style of frequent circadian clock alteration may contribute greatly to this problem. My father has been struggling with the disease and prevention is the key to avoid its debilitating complications. This award will greatly assist our effort in finding out the precise ways how our natural clock systems influence energy balance and advance our fundamental understanding of this system in human physiology and disease processes.
In what direction do you see the future of diabetes research going?
Biological clocks are present in every cell types in our body and they greatly influence overall energy balance. Currently, we are just beginning to elucidate the role of one specific regulator of the clock system, Bmal1, in brown fat formation. Our goal in the future is to decipher the participation of additional components of the clock network in controlling how our body respond to energy excess and devise strategies to target these specific mechanisms.
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