Kim, Young-Bum , PhD
Clusterin as a novel regulator of adiposity
General Research Subject: Obesity
Focus: Integrated Physiology, Integrated Physiology\Regulation of Food Intake, Obesity, Obesity\Pathogenesis
Type of Grant: Basic Science
Project Start Date: July 1, 2012
Project End Date: June 30, 2015
Obesity is a significant human health problem; its incidence is reaching epidemic proportions in many Western countries. Obesity is defined as a state of increased body weight, more specifically adipose tissue, of sufficient magnitude to produce adverse health consequences. Body weight and energy stores are tightly regulated, with either weight loss or gain producing concerted changes in energy intake and expenditure that resist the initial perturbation.
Leptin, an appetite controlling hormone released from fat tissues, plays an essential role in controlling food intake and normal body-weight regulation. It is now clear that leptin acts on specific brain regions to regulate food intake, energy expenditure and endocrine function. Obese state is associated with a decreased capacity of the body to respond appropriately to leptin. This situation is called leptin resistance, and the cause of this is not fully understood. Preliminary data have now identified a molecule called clusterin and its receptor LRP2 as a novel player in controlling appetite and body-weight homeostasis in brain. Importantly, inhibition of clusterin-LRP2 function in the brain results in a decreased leptin response, leading to leptin resistance and ultimately causing obesity. The studies in this proposal will extend these preliminary findings and clarify the role played by clusterin/LRP2 in the brain and in the development of obesity. These investigations could lead to the identification of an important new drug target in the prevention and treatment of obesity and type 2 diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
The proposed project covers the area of obesity research. Specifically, our research focuses on identifying the cause of leptin resistance, a major risk factor in developing obesity. Obesity is often associated with an eating disorder, which contributes to dysregulation of body weight homeostasis. It is clear that impaired leptin signaling in the brain causes excessive food intake, which then promotes body fat accumulation and weight gain. Preliminary data have now identified a molecule called clusterin, a plasma leptin-binding partner, as a novel player in controlling appetite and body-weight homeostasis in brain. The studies in this proposal will extend these preliminary findings and clarify the role played by clusterin in the brain and in the development of obesity. We will use state-of-the-art technology, including a genetically modified animal model and a virus-inducible gene-transfer approach in an in vivo context. These investigations could lead to the identification of an important new drug target in the prevention and treatment of obesity and 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?
The control of normal body weight is an important factor for preventing and treating diabetes. However, normal body weight is often difficult to maintain because of our lack of knowledge of the regulation of food intake and of body weight homeostasis in the brain. Thus, new therapeutic approaches are needed to promote effective weight reduction and to prevent metabolic-related diseases such as obesity and diabetes. My proposed work addresses these deficiencies in our knowledge by determining whether dysregulation of clusterin action contributes to the pathogenesis of obesity and metabolic-related disease. Studies in the proposal will lead to new therapeutic strategies for a treatment.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
As a scientist, I have had a long-standing interest in the areas of obesity and diabetes. My studies have been investigating the molecular mechanisms underlying insulin and leptin resistance seen in obesity and type 2 diabetes. Through my research efforts, I have committed to make scientific discoveries that will help the people with type 2 diabetes better understand the causes of the disease. This award will allow me to continue to pursue my scientific explorations. It is my hope that I will continue to develop novel approaches that lead to scientific discoveries and to contribute in the fields of diabetes and obesity with great impact.
In what direction do you see the future of diabetes research going?
Over the past decade, there have been intensive efforts to identify the cause of obesity and diabetes. Accumulating experimental evidence has suggested that high amounts of body fat in obesity accelerate insulin and leptin resistance, both of which are pathogenic features of type 2 diabetes. It is thus expected that future studies in diabetes will focus on the control of body weight and its dysfunction in the context of obesity. The beneficial information generated by this project will point to possible new approaches for treating and preventing obesity and diabetes.
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