IN 1998, THE NATIONAL INSTITUTES OF HEALTH proclaimed that obesity is a disease. The American Medical Association then followed suit. The World Health Organization made its own pronouncement, warning against “an escalating global epidemic of overweight and obesity”—and dubbed it “globesity.” As the U.S. and global medical communities jointly sounded the alarm about obesity, the task of understanding and containing this ever-growing health threat has been immense. To introduce our special report on obesity, Yale Medicine Magazine spoke to Nancy J. Brown, MD, the Jean and David W. Wallace Dean of Yale School of Medicine and C.N.H. Long Professor of Internal Medicine, about the public health danger posed by the condition and how YSM has responded. Why has obesity remained such an intractable health threat? Human bodies are wired to survive in times of scant resources, and we live in an environment with abundant food access. However, it’s not necessarily abundant healthy food access. In addition, most people are very sedentary. This combination of factors contributes to the epidemic of obesity. As an internist who specializes in hypertension, how do you view the health risks of obesity? Obesity has been tied to almost every disease—not just hypertension, but also diabetes, cardiovascular disease, cancer, and many others. Many of the drugs that we use to treat obesity today also have positive effects on cardiovascular risk. And it’s not clear whether those effects are related to weight loss or to a direct effect of the drug. I’m personally interested in that as a research question. But from a public health perspective, if we can reduce obesity, we can increase quality of life, as well as longevity. Recent studies have focused on pharmacological therapies. There is also a need to focus on the built environment and other approaches to reducing obesity. How have you seen this issue evolve over the course of your career? Our understanding of the mechanisms of obesity has evolved considerably since the time when I was first training. I think we viewed obesity as a character flaw and as a sign of weakness; we have now come to understand the central mechanisms that control appetite, the other factors that affect metabolism, and conversely the effects of obesity on inflammation and other systems. So there have been tremendous advances in our understanding. Do you believe that we’ve reached an inflection point in treating obesity? We have certainly reached an inflection point in that we have more—and safer—pharmacological tools available to us than we have ever had. We have a lot of considerations to weigh (no pun intended) around the utilization of these tools. For example, in whom should those therapies be used? How do we take into consideration things like pricing and affordability? How do we use those tools while still using multi-modality approaches to obesity that also include changes in lifestyle and habits? How is Yale School of Medicine making a difference in combatting obesity? Our faculty and our volunteers are contributing extensively, from very basic science in understanding what causes obesity, how obesity affects insulin sensitivity, how it causes inflammation, how it causes specific organ damage—all the way to leading the clinical trials of the latest pharmacological agents to reduce weight.