Dear Oprah,

I grew up watching you. Every day at 4pm after school, there you were. I had a subscription to O Magazine. You could interview and feel with your subjects like no one else. You broadcast and we all received.

And we watched your struggles with weight. We identified. I watched you pull that wagon of fat onto the stage in triumph. We commiserated when you gained it all back so quickly after the liquid diet. We agreed universally: if Oprah can’t lose weight with her resources, what hope do any of us have?

Years later, I watched you jogging along Lake Michigan, putting exercise at the core of your lifestyle. Recently, you finally achieved lasting weight loss with GLP-1s and wrote a book with an endocrinologist to share your success. I heard you say you finally have control over your appetite and food noise.

I didn’t analyze your words until now.

Now your journey makes me very sad, because I realize how much you were hating yourself for something you couldn’t control because of evolution.

I believe you carry two copies of a gene I study. Rs5522. I’ve been published on it.

This gene gave your ancestors a survival advantage. It helped them hoard salt and water when times were scarce. It likely helped some of them survive the brutality of enslavement and even the forced journey through the Middle Passage.

For you in modern life, this genetic gift felt like a curse. It caused a lifetime of difficulty as your body fought back against every investment in weight loss. We all saw it and said the same thing: if she can’t lose weight with her resources, what hope do the rest of us have?

You still blame yourself. You’re convinced GLP-1s curbed your out-of-control appetite. Maybe they helped. But your appetite was never the problem. Inflammation was.

In the presence of inflammation, your genes leak water into your tissues over time. That fluid looks like “fat.” It would have been more accurate if you had wheeled a wagon of water jugs onto your stage all those years ago.

Why did GLP-1s work this time? They lower inflammation. Yes, they affect appetite, but that was never the problem.

Think of The Biggest Loser contestants. They exercise all day and restrict food and drop weight rapidly, only to gain it back in most cases. Research shows the ones who keep it off exercise daily. But mathematically, that could never burn enough calories to account for the massive pounds lost.

So what was the diet and exercise doing? Lowering inflammation.

Why did contestants gain their weight back? Their genes fought back. The body raised the metabolic set point. Not through metabolism as we understand it. That word doesn’t mean what we think.

A lifetime of interviewing world leaders on thought and culture. Opening our eyes to truth. And yet this was a blind spot for you, like it was for all of us.

Now you have a platform that can change the world with one statement.

I’m asking you, dear Oprah, to bring attention to this. Because it’s more than “fat.”

It’s maternal mortality - Black women dying at 3-4 times the rate of white women because pre-eclampsia is this same mechanism.

It’s Long COVID - millions suffering because medicine doesn’t understand the genetic basis.

It’s chronic fatigue syndrome - 29 years of my life dismissed as psychological.

It’s billions of people blamed for bodies that are doing exactly what evolution designed them to do.

You have the reach. You have the credibility. You have lived this truth in your own body.

The research is published. The DOI is permanent. The mechanism is proven.

All it needs is your voice.

Sincerely,

Patricia Donnellan, MPH

Research: https://zenodo.org/records/19430550