News & Research

    Temple University School of Medicine, Philadelphia, Pennsylvania

Regulation of leukocyte trafficking in visceral fat depots: the role of adiponectin

General Research Subject: Obesity

Focus: Adipocytes, Integrated Physiology\Insulin Resistance, Obesity\Pathogenesis

Type of Grant: Basic Science

Project Start Date: January 1, 2012

Project End Date: December 31, 2014

Diabetes Type: Type 2 diabetes

Research Description

Obesity is a major health challenge facing the US population. Research has now shown that as weight increase to reach the levels referred as "overweight" and "obesity" incidence of and mortality from diabetes, cardiovascular disease and cancer increase. These complications of obesity have been widely linked to adipose tissue inflammation. In fact, the number of inflammatory cells is almost invariably elevated in the adipose tissue of obese individual and experimental animal models. Adiponectin is an abundant plasma protein secreted by adipose tissue that maintains a non-adhesive phenotype of the vascular endothelium thus attenuating leukocyte-endothelium interaction, the hallmark of inflammation. However, levels of adiponectin are reduced in obese subjects, which could sustain adipose tissue inflammation via infiltration of leukocytes. Accordingly, the long-term goals of this project are to define the mechanisms by which the various circulating forms of adiponectin prevent activation of leukocyte-endothelium interactions and infiltration of inflammatory cells in the adipose tissue itself. Overall, this research will uncover novel mechanisms of adipose tissue inflammation in obesity and it will provide a framework for developing new therapeutic strategies to avert complications in the obese population of the USA.

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?

Our research project focus on the role that adipose tissue dysfunction plays in inflammation, insulin resistance, and type 2 diabetes. Research has been made clear that obesity is associated with infiltration of leukocytes and leukocyte-derived inflammatory cells into visceral fat depots. The inflamed adipose tissue becomes dysfunctional and contributes to insulin resistance, diabetes and associated cardiovascular complications, whose incidence is gaining in the ever-growing obese population of the USA. The precise mechanisms by which weight gain initiates and maintains adipose tissue inflammation remain largely elusive, which limits therapeutic interventions in obese humans. Our working hypothesis is that consumption of obesogenic, high-fat meals acutely inflames the microcirculation of visceral fat depots, even prior to overt obesity and diabetes. As a result, adipose tissue is subjected to the damaging action of circulating white blood cells that become activated. The dysfunctional adipose tissue stops secreting adiponectin, a hormone which helps lower glucose in the blood. Accordingly, the long-term goals of this project are 1) to study the impact of high-fat meals and overt obesity on microvascular function; 2) to investigate the effects of leukocyte-endothelium interactions and adiponectin secretion; 3) to investigate the effect of adiponectin replenishing therapy in these studies.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Obesity and associated diabetes are a major health challenge facing the US population. Research has now shown that as weight increase to reach the levels referred as "overweight" and "obesity" incidence of and mortality from diabetes, cardiovascular disease and cancer increase. These complications of obesity have been widely linked to adipose tissue inflammation. Adiponectin is an abundant plasma protein secreted by adipose tissue that maintains a non-adhesive phenotype of the vascular endothelium thus attenuating leukocyte-endothelium interaction, the hallmark of inflammation. However, levels of adiponectin are reduced in obese and diabetic subjects, which could sustain adipose tissue inflammation via infiltration of leukocytes. Accordingly, the long-term goals of this project are to define the mechanisms by which the various circulating forms of adiponectin prevent activation of leukocyte-endothelium interactions and infiltration of inflammatory cells in the adipose tissue itself. Overall, this research will uncover novel mechanisms of adipose tissue dysfunction in obesity and it will provide a framework for developing new therapeutic strategies to avert complications in the obese/diabetic population of the USA.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

I have been always interested in studying how chronic metabolic diseases (e.g., obesity, diabetes and cholesterol) damage blood vessels and cause local and systemic inflammation in the cardiovascular system. The incidence of such conditions is so large in western countries that I always recognized the high social value of doing research in this area. In addition, I have lost several relatives because of vascular complication of insulin resistance and diabetes. Since I was a child I had to see close relatives whom I loved very much dealing with insulin injections and complications because of diabetes.

In what direction do you see the future of diabetes research going?

I believe that two major concept will emerge in the area of obesity/diabetes in the future: 1) People have to make the responsible decision of living a healthy life-style (proper diet and exercise). 2) The discovery of new genetic and biological markers of obesity/diabetes will help identifying those individuals who have a higher risk of developing vascular complications. Then, close monitoring of cardiovascular and metabolic parameters before the onset of overt disease may help prevent most of the life-threatening complication of obesity/diabetes.