Ania Jastreboff first met Oprah Winfrey in May 2024 while working together on a live virtual event called “Making the Shift,” in which Jastreboff explained the science behind obesity and answered questions from the audience.
Months later, Winfrey invited Jastreboff to her home in California to talk more about the topic for “The Oprah Podcast.” The plan was to record a 90-minute conversation for two podcast episodes about the evolving science of obesity medicine, including obesity medications.
Their conversation went long. In fact, they recorded for about four hours total. So, while sharing a meal afterward, Winfrey proposed an idea to Jastreboff.
“She turned to me, and said, ‘You should write a book. I will help you,’” said Jastreboff, the Harvey and Kate Cushing Professor of Medicine and professor of pediatrics at Yale School of Medicine. “In that moment, I thought, ‘This could help millions of people,’ and so the answer was clear.”
Last month, their book, “Enough: Your Health, Your Weight, and What It’s Like to Be Free” (Simon & Schuster), hit the shelves of bookstores across the country and became a New York Times best seller. It examines the biology of obesity — and offers a new way forward for obesity treatment and overall health.
Jastreboff is also the director of the Yale Obesity Research Center (Y-Weight), co-director of the Yale Center for Weight Management, and medical director of the Yale Stress Center.
In an interview, she discusses her new book with Oprah and her research on obesity medications; the interview has been edited for length and clarity.
When it comes to weight, how do our bodies work with us but also against us?
Ania Jastreboff: Our bodies are super smart. They figured out ages ago that in order to survive, we needed to store fuel, and we store that fuel efficiently when we store it as fat. Fat is a very good thing because it enables us to survive as a species. So how does our body determine how much fat to store? This is controlled by our brains and has been referred to as the body fat set point. In the book, we call this the Enough Point. Your brain determines your Enough Point. But how does the brain know what that Enough Point should be? It gets inputs from our body via various signals. These signals include hormones, specifically nutrient-stimulated hormones, or NuSHs for short, such as GLP-1 and GIP. These NuSHs communicate: “I’m hungry,” “I’m full”, “I’m craving this,” “I need to eat more.” They communicate to the brain, and then our brain gets the information it needs to regulate and maintain an Enough Point.
It’s not a matter of choice. It’s not a matter of willpower. It’s not a moral failing. It’s a disease just like any other chronic disease.
Now, you might wonder, “Well, we have this incredible biology. Why do so many people have obesity? Why do so many people carry extra or excess fat, which then can cause significant detrimental impacts on our health?” Well, it’s our obesogenic environment, an environment that is filled with ultra-processed food, lack of sleep, lack of physical activity, lots of stress, all these things drive up that Enough Point. They drive up the Enough Point on a population level, and that is why so many people have obesity or are overweight. We have to change it to a healthier environment, and that is very important for prevention of obesity. But once somebody develops obesity, we need to provide treatment options and tools if they are seeking treatment for the disease.
Why is there so much stigma surrounding weight?
Jastreboff: We need to shift the culture from blame and shame to one of compassionate care for people living with obesity — we can begin to do so through an understanding of biology and an understanding that obesity is a disease. It’s not a matter of choice. It’s not a matter of willpower. It’s not a moral failing. It’s a disease just like any other chronic disease. Just like diabetes. Just like heart disease. We should be treating obesity as we treat these other chronic diseases.
Hopefully, this book is a part of that shift. This book is for people living with obesity, people who love someone who has obesity, people who are interested in learning more about health. This book is an accessible resource that provides the opportunity to gain a deeper understanding of obesity biology. It’s one thing for someone to say obesity is a disease, it’s another for us to share, “Well, this is why it’s a disease. Here’s the biology. Let’s see how we can understand it together.” And, if we can understand it, then we can find ways to treat it.
You’ve been studying GLP-1-based medications for more than a decade and a half now. How have these drugs transformed our understanding of weight and obesity?
Jastreboff: There are transformative moments in medicine like the discovery of insulin and the discovery of penicillin. These therapeutics saved millions of lives, and they also helped us learn about the biology of the diseases they were treating. I think that these new GLP-1-based medications are doing just that. If we can treat obesity — the root cause or primary contributor of heart disease, of type 2 diabetes, of obstructive sleep apnea, of so many diseases — then we can potentially prevent, mitigate, or treat over 200 obesity-related diseases.
GLP-1-based medications are also teaching us about the biology of obesity. I’ll give you an example: Food noise. We did not know that food noise existed until our patients started taking the medicines. Patients started sharing with us that suddenly, their thoughts were cleared of the persistent, intrusive, disruptive thoughts of food that they did not realize had been there until they experienced the peace of silence. The medicines taught us this. They taught us about food noise, a manifestation of our brain’s biology trying to pull up to a higher Enough Point. That’s a piece of the biology of obesity. There are many other things the medications are teaching us and will continue to teach us about the biology of obesity.
Where do you think the field of obesity science is going next? What should we expect to see in the next few years?
Jastreboff: It truly is a transformative time. It’s a transformative time because these medications are teaching us about the biology of obesity and providing highly effective treatments for obesity. The pace is frenetic.
The nutrient-stimulating hormone-based therapies, or NuSH-based therapies, including GLP-1-based therapies, are just one class of medications. But just as for other diseases there are many classes of medications, so too there will be many classes of medications for obesity treatment.
There are several reasons why this is important. One of them is that not everybody responds to the current therapies. That’s because there’s not one type of obesity. It’s a heterogeneous disease, which will require different type of treatment. We shouldn’t be surprised that people need different types of treatments for their specific obesity.
The way that things are moving and progressing, we already have highly effective weekly injectable medications. We will have oral medications, one of which is already FDA-approved. There are also monthly injectable medications under development. I think where we’re moving to is to have the type of choices and treatment options as we do for a host of so many other complex chronic diseases. There’s so much hope for patients living with obesity.
Anything else you hope readers take away from the new book?
Jastreboff: The goal of treating obesity is improving and optimizing health. Just in the last three years or so, we’ve had many studies demonstrating how treating obesity with obesity medications can impact obesity-related complications and diseases. Treatment with semaglutide has demonstrated decreases in the risk of a second cardiovascular event in people who have had a prior heart attack or stroke and the medicine is now FDA-approved for such patients with cardiovascular disease. Treatment with tirzepatide has demonstrated improvement in obstructive sleep apnea and the medicine is now FDA-approved for sleep apnea as well. These medications also improve blood pressure. They improve blood sugars. They improve lipids. They improve kidney disease and liver disease. There are many health benefits that are being demonstrated with these medications, all of which underscores that treating obesity improves overall health. Treating obesity effectively has the potential of improving the health of our world.
