Cohen, David E., MD, PhD
Them1-mediated control of energy expenditure in brown adipose tissue
General Research Subject: Obesity
Focus: Adipocytes, Integrated Physiology, Integrated Physiology\Fatty Acid Metabolism, Obesity, Obesity\Pathogenesis
Type of Grant: Mentor Based Minority Postdoctoral Fellowship
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
Obesity is a major health problem that predisposes to type 2 diabetes. Human beings harbor two distinct types of fat. White fat is primarily a long term storage depot for energy and is present in excess amounts in obese individuals. By contrast, brown fat helps to consume excess energy by generating heat. Obesity may be due at least in part to inadequate activity of brown fat. The investigator's laboratory has identified that a protein named thioesterase superfamily member 1 (Them1), which is enriched in brown fat, reduces energy expenditure in mice. Consequently, mice that are engineered to lack Them1 become resistant to experimental obesity and diabetes.
There are four main objectives of this research project. The first is to define the molecule within brown fat that binds to Them1 and activates its function. The second is to determine the effect of Them1 on the compositions of membranes in brown fat cells. The third is to understand how Them1 limits the expenditure of energy. The fourth is to determine how Them1 functions within brown fat cells to reduce energy consumption. These objectives will be achieved by using sensitive biochemical and biophysical methods to study the structural and functional characteristics of purified Them1. In addition, mice will be employed that are genetically engineered to lack Them1, as will brown fat cells that are isolated from the mice. These studies should reveal new mechanisms that control caloric consumption by brown fat and could identify Them1 as a pharmaceutical target to treat obesity.
Mentor: David E. Cohen, MD, PhD Postdoctoral Fellow: Kristal Maner-Smith, PhD
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This research will explore the role of a specific gene known as Thioesterase superfamily member 1 (Them1) in the regulation of energy expenditure in the body. Current research suggests that brown fat plays an important role in regulating metabolism and body weight in humans by burning excess calories to create heat. Our research in mice has demonstrated that Them1 reduces energy expenditure by brown fat, presumably allowing mice to conserve calories so that the animal can survive when food is scarce. On the other hand, when food is abundant, Them1 appears to contribute to the development of obesity and diabetes. Our project is aimed at understanding the mechanisms by which Them1 controls energy expenditure. This understanding could lead to drugs that inhibit Them1, which should increase energy expenditure, leading to reductions in body fat and improvements in 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?
This project offers an approach to the treatment of type 2 diabetes that is not currently available. It is anticipated that drugs promote the consumption of excess calories by brown fat should improve glucose control in individuals with diabetes. It is also possible that this approach could promote weight loss in overweight persons.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Type 2 diabetes is a devastating disease, and its prevalence is increasing at an alarming rate. I am a physician-scientist who is dedicated to the understanding and cure of metabolic diseases. In addition to my own research, I aim to contribute to the cure of diabetes by training the next generation of researchers with similar goals. This Mentor-Based Postdoctoral Minority Fellowship Award will support both of these important objectives, as well as promote diversity among emerging scientists.
In what direction do you see the future of diabetes research going?
Although very important advances in medical research have already expanded our ability to treat diabetes, a key future goal must be prevention. Type 2 diabetes is very closely linked to overnutrition and obesity. Improved treatment modalities to reduce body weight, while improving nutrition represent a critical frontier in diabetes research.
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