Moment 209: The Real Reason You’re Gaining Weight (Even If You’re Exercising!)

Steven Bartlett (0:00)

With my genetic makeup, Yep. how might there be differences in my genetic makeup that make my relationship with food and eating and weight loss different from yours?

Giles Yeo (0:12)

Oh, okay. I probably don't have as good an answer. Genetics does not have as good an answer about why different people eat differently, aside from cultural differences at the moment. Okay, so the genetics. The reason behind that is because it's very difficult to accurately determine what someone has eaten in order to do genetics. What we do know, because we can actually observe, is how people of different ethnicities are susceptible to different diseases. So famously, East Asian people, people that look like me, South Asian people, Indian, Pakistanis, Bangladeshis, cannot get as large, BMI-wise, before becoming at risk of type 2 diabetes, right? Compared to white people, Polynesians famously, who can get pretty large, before they actually end up getting diseases. So that's a classic example, where this is why South Asian people, East Asian people have a higher predisposition of diabetes, even though obesity is not particularly a big thing in their cultures. But then you then begin to look at body shape, that does matter as well. Where do you put your fat? Do you tend to put the fat on your bum, on your tummy, how tall are you, how short are you? And all of these things, which we can see visually, we can see, there are people who are then susceptible or not susceptible to specific diseases. Other things you can't see. Why are African Americans, for example, more likely to end up with cardiovascular heart disease, less likely with diabetes? Whereas, why are Indians, you know, more... And so you then begin to ask the question, and there we have genetics.

Steven Bartlett (1:56)

What about in terms of this obese gene? I read in chapter two of your book that there is a gene for obesity.

Giles Yeo (2:04)

There are more than a thousand genes for body weight. The obese gene in chapter two, which I talk about, is this leptin gene. It's this gene which lets your brain know how much fat you have. So that's the exact gene. Leptin is the gene that I'm talking about in chapter two with the obese... It's called the obese gene because the mouse was called obese. There was a lack of imagination because the mouse was a naturally occurring mouse that had a mutation in the same gene. Scientists found out what that was and then found out that it was conserved in humans. And that's where my boss, Steve O'Rathley, then came in and found that that gene was also mutated in some humans. So that's the obese gene.

It's the fat gene, fat gene, meaning gene from fat, that let's your brain know how much fat you have.

Steven Bartlett (2:50)

And is that possible to be not just on or off, but slightly defective? So some people can just get a little bit more hungry than others, or is it a binary thing where it can be on or off?

Giles Yeo (3:00)

So leptin, for whatever odd reason, is pretty much binary. So if you have a little bit of it, you're fine. If you have none of it, you're not. However, there is obviously a pathway. Leptin signals to the brain, which signals to something else. And there is another gene that I looked at called MC4R. It's part of the pathway. It's part of the same fat sensing pathway. That is a rheostat. It's like a thermostat. And so, for example, we have found thousands of different mutations in this gene. And you can imagine that depending on the severity of the dysfunction, some are completely dead, some are 70% functional, we can predict how much someone will eat in a test buffet meal scenario if they have a 50% functioning gene versus a zero functioning gene. And we now know that 0.3% in this country at least, so 200,000 people in the UK, a million people in the United States, will carry mutations in this MC4R gene, making them more likely to end up with obesity.

So that at 18 years old, if you carry a mutation in this MC4R gene, you are on average 18 kilos heavier, 40 pounds heavier at 18 years old on average. And that's 200,000 people in this country. So it's not super common, right? It's still 99.7% of the people's body weight is not determined by this. But there are a lot of people's body weights who are dependent on this specific gene. But it is a tunable system. So it's a little bit or a lot means that you're either slightly heavier or a lot heavier.