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Rachel Uda January 22, 2026 at 3:47 AM

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Oprah's Biggest Lessons About the Biology of Obesity

Oprah Winfrey opens her new book by looking back at one of the most painful moments of her career. It was 1985, she was 31, and was set to make her first appearance on The Tonight Show. Joan Rivers was the guest host, and instead of discussing Oprah’s talk show, the comic made the segment all about her body.

“I’ll never forget the moment she looked at me and said, ‘How’d you gain all the weight?’”

It was the first in a long line of public humiliations, the icon writes — from David Letterman making fun of her for an entire year to the crude tabloid headlines: “Oprah Fatter Than Ever,” “Oprah Warned: Diet or Die.”

In Enough: Your Health, Your Weight, and What It's Like To Be Free, Oprah opens up about the decades she spent crash dieting, the shame she felt as her weight yo-yoed, and how, with the help of GLP-1s and experts like Dr. Ania Jastreboff (who helped co-write the new book), she was able to see that it wasn’t her fault. She had a chronic disease — obesity — and she needed medication to silence the food noise and eventually “say yes to life.”

We spoke with Dr. Jastreboff about the biology of obesity, how the “enough point” dictates how much fat we store, and much more.

How did you come to co-write this book with Oprah?

Dr. Jastreboff: We had just recorded two podcasts. We were meant to record for 90 minutes, but we taped for nearly four hours because there was just so much to say. Afterwards, we were eating together and Oprah turned to me and said, “You should write a book. I’ll help you.” In that moment, I thought this could help millions of people. She’s been named and shamed publicly for her entire career, and it’s incredibly unfair and unjust that she was blamed for having a disease. She’s turning her pain into a gift for people with obesity and giving people with obesity a voice.

Can you explain the biology of obesity as a disease?

Our bodies are incredibly smart, and they recognize that in order to survive, we had to have a way of storing fuel. Our bodies store that fuel as fat. But how much fat do we need to store? Our brain regulates that amount, and we call this the "set point," or the "enough point." Our bodies defend that amount of fat, which is a good thing because it allows us to function without constantly having to fuel. But for some people, that enough point is elevated, so many Americans are carrying extra fat that spills into their organs and can negatively impact their health.

In the book, Oprah talks about how her enough point is 211 pounds. Can you explain how the body defends that level of fat, as you said?

Oprah shares a story in the book about how she would hike miles and miles every day and eat very healthfully in order to lose weight. She has so much grit and conviction, but in the end her biology still wins and she regains the weight. This is what happens when somebody with obesity is trying to lose weight with caloric restriction. A diet doesn’t change their enough point, so what happens is the body becomes more efficient and burns less fuel to do the same tasks. So Oprah’s body burned fewer calories to do the same hikes, while at the same time, it made her more hungry and made her want to consume more food.

These cravings are known as food noise. Can you break down what causes that?

If somebody has obesity and they’re living below their enough point, their body will do what it can to get them back up because it thinks they’re in danger. That manifests as food noise — pervasive, disruptive, and persistent thoughts of food. My patients will tell me that they wake up in the morning and their first thoughts are about food, or that leftover cheesecake in the fridge. Or they have a report due at work and they can’t focus because they keep thinking about what they’re going to eat for lunch. The thoughts are very intrusive. Oprah describes how she felt so much freedom from not hearing the food noise and having the peaceful silence and brain space to be able to think about other things.

The obesity medications are helping us to learn so much about the biology of obesity. We didn’t know that food noise even existed until our patients were coming to us and telling us about how these persistent thoughts went away once they went on the GLP-1 treatments.

Is a high body fat set point something people are born with, and does it change?

On a molecular level, we don’t know how the set point is set and how it changes over our lives. We do know that the environment impacts it, and that’s what we’re seeing in our population. We live in an obesogenic environment, where ultraprocessed food is widely available, most of us don’t get enough sleep or physical activity, and we're dealing with a whole lot of stress. That’s led most Americans to carry extra fuel in the form of excess fat. We also see it shift naturally during certain periods. Our bodies start to store more fat during puberty, pregnancy, and menopause.

How do the GLP-1s work?

The brain gets information about the body through different hormones. The GLP-1 hormone, and others like the GIP, are called nutrient stimulated hormones, or NUSHes, which are secreted when we eat food. Obesity medications target the same pathways these hormones work to reduce appetite in the brain.

Are there other obesity medications in development?

The NUSH-based therapies are the first highly effective class of medications to treat obesity. But in the future, I think there will be hundreds of medications to treat obesity. That’s really important because some people do not respond to what’s currently available.

There are also medications that are looking to preserve muscle mass while optimizing fat loss, and other mechanisms that are being explored. There are over 200 different medications for high blood pressure, and likewise, I think we’ll see many more options for patients with obesity.

Do you have to stay on a GLP-1 for the rest of your life?

Obesity is a chronic disease — and it necessitates chronic treatment. If we think about other chronic disease treatments (like blood pressure medications, for example), when you start taking those drugs, your blood pressure decreases. But if you stop, your blood pressure goes back up. It’s the same with obesity. These medications work by lowering the set point, and the weight loss occurs because of that. When a patient goes off the medication, the set point goes back up and the weight is regained.

What are some of the side effects of GLP-1s, and do you have any advice for how to manage them?

The most common side effects are gastrointestinal, including nausea, diarrhea, or constipation. The first tip is to start low and go slow with a GLP-1. Work with a healthcare provider and start at the lowest dose of the medication and increase it very slowly. Then I’d advise not to eat past the point of fullness, eat smaller portions but more frequently, and note which foods exacerbate your symptoms in a food diary. Once your weight plateaus, you should be able to eat those foods again without symptoms.

I’d also make sure to drink lots of water. Food contains water, so if you’re eating less, you’re going to be consuming less water. Staying well hydrated can help with nausea.

And of course, my final piece of advice is to talk to a healthcare provider if you’re experiencing side effects. They’ll be able to guide you through some of those issues.

This interview has been edited for length and clarity.

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