Targeting Angiogenesis as Treatment for Obesity
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Worldwide, more than 1 billion adults are overweight, and obesity constitutes a key contributor to chronic disease. The conventional wisdom is that this rising epidemic reflects societal adaptation to a sedentary lifestyle and nutritional transition to overconsumption of inexpensive and calorie-dense diets. Implementing behavioral lifestyle modifications to promote weight loss and maintenance, including physical activity and a healthy diet, constitutes a major clinical challenge and remains difficult to achieve. Similarly, there is concern about the safety and potential long-term complications associated with enforcing caloric restriction through bariatric surgery. Finally, the currently available two pharmacological agents, orlistat and phentermine, have limited efficacy and side effects. Consequently, there is an unprecedented need for the development of effective and safe weight loss strategies, and understanding the physiology of obesity may provide novel therapeutic opportunities.
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In the current issue, Cutchins et al identify a previously unrecognized mechanism underlying adipose tissue expansion during obesity.1 The authors first demonstrate that the inhibitor of differentiation-3 (Id3) is expressed in adipose tissue and induced during obesity. Fractionation and immunohistochemistry of the adipose tissue revealed that high-fat diet feeding and the ensuing development of obesity results in increased Id3 expression in endothelial cells. Important functional experiments demonstrated that genetic deletion of Id3 in mice prevents adipose tissue expansion during …