The past 30 years have produced an epidemic of obesity — mostly because evolution did not prepare us for so many calories and so little physical activity. Dr. Louis Aronne, a leading authority on obesity, explains how a period of caloric excess can damage the neural connections that manage your metabolism, throwing your weight regulation out of whack. More importantly, he talks about the new drug that tackles obesity at two different hormonal sites and promises to become an actual “weight loss pill.” Plus… the real reason to skip the bread basket (it’s in your brain)

Phil Stieg: Hello and welcome. Today I’m with Dr. Louis Aronne a leading authority on obesity and its treatment. He’s the Sanford I Weill professor of metabolic research at Weill Cornell Medical College and directs the center for Weight Management. He’s authored more than 60 papers and book chapters on obesity, and he edited the National Institutes of Health practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Dr. Aronne, thanks for being with us today.

Louis Aronne: Thank you, Dr. Stieg, for having me on. It’s a pleasure to be here.

Phil Stieg: Let’s get everybody on the same page here. So what is the definition of obesity?

Louis Aronne: Well, the definition of obesity is excess body fat, and it’s a continuum. So the amount of fat you store is a continuum. And we have cut off points where we define obesity. And by the way, the convention now is to say that someone has obesity, not that they’re obese.

Phil Stieg: I see.

Louis Aronne: Right. So they have a brain tumor. They’re not a brain tumor. He’s a tumor. You got that?

Phil Stieg: It’s good.

Louis Aronne: And the reason is because we now know that obesity is a disease. So like other diseases, you can have obesity. You’re not obese.

Phil Stieg: All right, you know, I’m a brain guy, so tell me, how does having obesity affect the brain?

Louis Aronne: There are a number of ways that obesity affects the brain. So I guess the most important thing is that – no matter what it looks like, obesity is a disease of the brain.

Phil Stieg: Well, you’ve written a lot about the fact that obesity is not a weakness or a lack of willpower, but it’s an endocrinologic problem. What is that endocrinologic abnormality?

Louis Aronne: So what research has shown so what research has shown that fattening food and lack of exercise clearly contribute to obesity. ut maybe not in the way that most people think. It looks like periods of calorie excess may damage nerves in the hypothalamus, the critical weight regulating part of the brain and reduce the brain sensitivity to hormones that regulate body weight.

So the idea is that by eating fattening food, your brain can’t tell how much you’ve eaten and how much fat is stored. How does that happen? It looks like calorie overload damages the energy producing parts of the nerves. They’re a group of nerves that are very sensitive. Too much energy comes in too quickly. The nerves actually deteriorate. Some die, others become resistant to these hormones. So the process is one of continual increased resistance. And so that when you think about the weight set point, one thing people have noticed for hundreds of years is your weight only goes up. It doesn’t go down on its own. That’s very rare unless you have an illness. And if you ask why that is, we think that it’s because of continuing damage to this and other groups of neurons that are critical for body weight regulation.

Phil Stieg: So how does the brain regulate obesity? If there’s a need for energy intake, energy expenditure, what’s the relationship between the brain and the body in that regard?

Louis Aronne: So the system is perfectly regulated. If you think about the number of calories you take in in a year, it’s on the order of hundreds of thousands of calories a year, right. 2000 to 3000 calories a day, 365 days a year. You’re talking about hundreds of thousands of calories. And yet the average weight gain that occurs is about £1. It’s a very small fraction, much less than 1%. So it’s a primarily regulated variable of the body, like your blood pressure, your pulse, your temperature, your blood sugar, your sodium. Weight is carefully regulated, But there’s a difference, and that is there is a health advantage to storing extra calories as fat.

So when you think about survival in the wild, right, we’ve only had a society that can deliver food instantly for the past few years, before that, you had to go out and get it yourself. And then you go back 150 years ago, you had to go out and kill it yourself, or you had to harvest it yourself. And if you wanted bread, they handed you this scythe to go out and cut the wheat. Then you had to go and grind it.

I mean, it was a big process to get calories. So systems have developed to help with survival during periods of famine.

In fact, we have a saying in the field of obesity research that Darwin got it wrong in looking at survival advantage. It’s really not survival of the fittest, but survival of the fattest, because the fattest are the fittest. In any wild environment, you’ll survive periods of famine, which is really the most –

Phil Stieg: Fat, but not obese.

Louis Aronne: Well, so here’s a good example. Let me give you an example. That’s right. Extra weight store but you can see that obesity has only occurred as a public health problem in the past 20 or 30 years because for the rest of the history of man it wasn’t possible to get enough calories and do little enough exercise to develop obesity.

Phil Stieg: So you’ll have to forgive me then. I thought that there was always this big deal about body mass index.

Louis Aronne: That’s right.

 Phil Stieg: Is that the criteria that you use for these different levels of having obesity?

Louis Aronne: So the formal definition of obesity based on the body mass index, which is a way of correcting your weight for your height, is a body mass index of 30. That’s the point at which we consider someone to have obesity. So why 30? If you look at the risk of developing type two diabetes, for example, if it’s one at a BMI of 22, which is considered to be in the normal weight range. So 20 to 25 is normal. 22 is in the middle. Let’s give that a risk of one. If your body mass index is 30, your risk is 20, 30, 40 times greater than it is at the baseline.

 Phil Stieg: So is this something I can easily do at home? Calculate my body mass index or my BMI?

Louis Aronne: Absolutely. The easiest thing in the world.

Phil Stieg: What do I do?

Louis Aronne: What you do is you look at a chart and you look at your height, and you may want to go measure yourself because your height may have changed. And then you get on a scale and see how much you weigh. And the easiest way to do it is to look at a chart or to go to a BMI calculator that you can find online. The formula is a little bit complicated. It’s your weight in kilograms over your height in meters squared. Most people don’t have the patience to do.

Phil Stieg: You have obesity and be healthy.

Louis Aronne: There are people who have an increased body mass index who are healthy. There’s no question. So the first example I’d give you are professional athletes. They have a high body mass index. And if you look at sumo wrestlers, sumo wrestlers have a very high body mass index, but they have much higher proportion of muscle to fat than you would expect in somebody of that body mass index. But by and large, people with a high body mass index have health problems, increasing health problems, as their body mass index increases.

Phil Stieg: I would think that there are more joint problems, back problems, aside from the diabetes we talked about earlier. And then I guess I would ask you, do the large football players and sumo wrestlers, do they have a normal life expectancy?

Louis Aronne: Well, that’s a really good point, Phil. It’s been shown that if you look at football players, the lowest life expectancy occurs with offensive linemen, then come defensive linemen and the longest lived are the defensive backs who are the smallest. So if you look at the average offensive and defensive linemen, their life expectancy is in the high fiftys. And what the NFL has done now is to screen them for problems like sleep apnea, which in the past was a leading cause of death for professional football players. But now with our understanding that basically every football lineman has sleep apnea until proven otherwise.

Phil Stieg: You’ve done some recent research on a drug, Tirzepatide. Tell us what that is and what your findings have been.

Louis Aronne: Tirzepatide is a new compound. It was recently approved by the FDA for the treatment of type two diabetes. It’s in a class of drugs called an encryption analog. The unique thing about this compound is that it hits two different hormonal sites. It hits a hormone receptor called the GLP one, glucagon-like peptide. One receptor, glucagonlike peptide is a hormone that’s released from your intestine when you eat food it’s one of the hormonal signals that tells your brain how much you’ve eaten. So if you eat food, your GLP one levels go up. You feel full. As time goes on, they go down, you start feeling hungry again.

So, the former GLP one medicines that we had for treating diabetes have now been approved for the treatment of obesity because they make you feel full. They make you feel like you’ve already eaten. But terzepatide hits two receptors. It hits another receptor called GIP. And what we’ve learned is that hitting two receptors is better than hitting one receptor. And what has resulted is weight loss that is on the order of magnitude of bariatric surgery. So if you look at bariatric surgical procedures, a lap band produces about 17% weight loss. A sleeve gastrectomy, which is the most commonly performed procedure, about 25%. If you look at results with tirzepatide, it produced 22 5% weight loss, almost the same as the most commonly performed bariatric procedure.

Phil Stieg: How does this drug then affect the emotional component related to both the satisfaction from eating and the benefit from weight loss?

Louis Aronne: What we have found so far? So this medicine has been around for just a few months, three or four months. And what we’re seeing on part of many people who are trying to lose weight is what I would describe as relief. In other words, they’ll tell us this is what a normal person must feel like when they eat. Instead of eating and then wanting to eat more and more and more when I know I shouldn’t be eating, I eat. I feel full, I stop eating. It’s unbelievable. I haven’t been able to do this before. So it helps people to comply with a diet. It’s not instead of a diet, I mean, our dietitians love medicines like this. And there are other medicines like this. There’s one called Wegovy that is so popular that it’s sold out, you can’t even get it. And it does something that is very similar, that’s for weight loss. That is what is currently available for weight loss. Wegovy is now become the most popular weight loss medication in the history of obesity. And this happened over the course of the past year. So much so that the company that makes it has people come around, tell us to stop prescribing it because they don’t have enough of it.

Tirzepatide is the next generation, and the FDA has given it a fast-track designation for approval for obesity treatment because it is such a breakthrough and that it’s even more effective

Phil Stieg: How do you see this being utilized worldwide? Because, as we said at the top of the show, obesity is a worldwide problem. Is this drug going to be accessible? Is it affordable? How do we even inform people that it’s available to them?

Louis Aronne: Right now, it just came out. It’s very expensive. As many medicines are over time, with increased availability and other compounds, there’ll be competition. The price will come down quite a bit. It’s possible that countries will take matters into their hands and say, this is so important for the health care of our country that we are going to make this available for a lower price.

But it brings up an important point, which is, what’s the correct treatment paradigm for treating obesity? Do you wait until people are severely ill and have a body mass index, say, of 40 and above before you treat them? Or do you begin treating them with tiny doses of medicine when they have a BMI of 25? And I think that as time goes on and we begin to treat this generation of people with severe obesity, we’re going to shift to something that’s more like hypertension, where we treat people at a certain point, BMI of, let’s say, 27,

Phil Stieg: Catch it early,

Louis Aronne: Catch it earlier, use a tiny dose of medicine and never let it get out of control. That’s what really changed things with hypertension. When people first started treating hypertension, they waited until they went into heart failure or had a stroke, and it was too late.  The damage was done. We need to start treating obesity much, much earlier.

(Interstitial Theme Music)

Narrator: Ever wonder why most restaurants put a basket of bread on the table as soon as you sit down?

Some say it is a sign of hospitality dating back to seventeenth century roadhouses and taverns. Other (more cynical ) patrons assume the bread is there to give bored customers something to do while waiting for the waiter to finally take their order, or to fill them up so they don’t notice small entrée portions!

Etiquette manuals tell us that one should always refrain from eating the bread until the entrée arrives –

(Voice of Etiquette Book)

… “bread should always be eaten with the meal. It is rude to fill up on it beforehand”…

Narrator: Rude or not, many restaurant patrons end up eating the bread first. But should they?

In 2014 Dr. Louis Aronne’s lab at Weill Cornell Medicine designed a study to see if the order in which foods were eaten had an effect on blood sugar and glucose levels in patients with Type Two Diabetes.

A group of eleven patients were fed identical meals one week apart. The only difference was the order in which they ate the various courses.

During the first meal they were instructed to eat all the carbohydrates (in the form of bread and orange juice) first and then 15 minutes later have the rest of the meal, consisting of grilled chicken, steamed broccoli and a salad.

A week later the same group enjoyed the same meal in reverse order; chicken, broccoli and salad first, followed by bread and beverage.

During both meals their blood sugar and insulin levels were measured over the course of two hours. The results were striking.

When people ate the bread first, their blood sugar rose steeply from 106 to 156 in a half hour, topping out at nearly 200 after just one hour before then starting a swift drop back down.

Doing the reverse the next week – starting with chicken and vegetables – their blood sugar levels rose very gradually, never getting as high as it did the week before. Lower blood sugar levels are good for those with diabetes, and avoiding peaks and crashes is good for all of us.

Dr. Aronne concludes that it’s hard to tell someone trying to manage their weight and blood sugar “don’t eat that” but, given these results, it might be much more reasonable to say, “eat this before you eat that”.

Phil Stieg: There is a social movement about body positivity, which I want to know, do you think that that promotes well, it promotes embracing all body types. But do you think that that in essence then might have an effect – a negative effect on overall health?

Louis Aronne: So body positivity, I’m all for body positivity. We are not trying to make everybody look model thin. But we want people to be at a healthy body weight for their own good health. We think that people deserve to live a long and healthy life. And it turns out that if you’re at your highest body weight, whatever that is, you may not live your longest life if your weight is in the category of obesity, and for some people, even overweight, if you lose just 5% of your body weight, if you weigh 200pounds, you lose 10pounds. So you’re far from being thin. That reduces your risk of developing diabetes by 50% 50%. I mean, that’s a lot of health benefit for not a lot of weight loss.

Phil Stieg: I’m curious about the emotional responses to having obesity and how you go about treating that. Obviously, you try to treat the underlying issue, which is obesity, but that can be a difficult, long, prolonged problem. So how do you go about treating the emotional components?

Louis Aronne: The most important thing about treating obesity is understanding that it’s not the patient’s fault. In the past, people with obesity were blamed. Don’t you know that this isn’t good for you. Don’t you know your life would be so much better if you would just lose weight? And the fact is that people with obesity do know that. They want to lose weight in the vast majority of cases, but they can’t because something physical is holding them back.

Patients used to tell me, if I could only lose weight, my depression will go away. And you know what? It happens a lot of the time. I am just shocked. I never thought that a woman who had obesity said, you know, if I lose weight, I know that my depression will go away. Sure enough, their depression went away. Their feelings of negativity, their feelings of self-loathing. I mean, it’s kind of miraculous when you’re able to get people to lose weight like that.

Phil Stieg: What are your thoughts about the way Hollywood portrays having obesity? I was thinking about this interview and Laurel and Hardy, the pudgy guy, and John Candy, the happy guy that obviously was overweight. And then Martin Lawrence playing the heavyweight grandmother. Do you think that is something that should be dealt with, thought about, and maybe not pursued?

Louis Aronne: You know, that was the way that people thought about things back then because of a lack of understanding of the problem. Now that we are knowing better, I think these are issues that we should have in the rearview mirror. That kind of comedy should be in our rearview mirror.

The patients we see are incredibly talented, creative, productive. The only thing they can’t handle is their weight. And then when you ask, when you really get down to what’s going on, it’s something physical that’s happening. It’s like wanting to be taller. You can’t be promoted because you’re not tall enough. I mean, maybe that does happen. I’m sure there are people who haven’t been promoted because they’re not tall enough. But it’s well documented that if you have obesity, there’s a good chance that you will not be promoted compared to somebody of normal weight. There are more opportunities for people of normal weight.

Phil Stieg: I got to ask, being an internist and your life’s commitment to managing obesity, what are your thoughts about the surgical procedures, the stapling, the stomach size reduction in that?

Louis Aronne: So bariatric surgery has really been critical to our understanding of obesity and to paving the way for demonstrating how much health benefit can be achieved from weight loss. Without bariatric surgery, we would be nowhere. And many, many people have benefited from bariatric surgery. And unfortunately, only a few percent, two or 3% of people who qualify for bariatric surgery have gotten it. And there are a variety of reasons. But the bottom line is there’s tremendous bias against physical treatments for obesity because people are blamed for having obesity and it’s seen as being a shortcut. So doctors don’t refer patients the way they should, but even if they do refer patients, then the patients themselves say, Well, I would do it, but it’s a shortcut.

For many years, surgeons who performed bariatric procedures were seen as second-class citizens. You didn’t see them at major academic centers. However, now there is a presence of bariatric surgery in major academic centers throughout the country, but it’s still not reached the level of acceptance of other procedures. So, for example, there are insurance companies that do not cover bariatric surgery. I mean, think about a patient with a BMI of 50 and all kinds of other problems, and you can’t get bariatric surgery which would take care of all them. That still exists. It’s crazy. But that still is out there.

Louis Aronne: The bias, I believe, is rooted in the belief that people could just control their weight if they wanted to. If you really wanted to, you should be able to do it, and we see it.

Phil Stieg: People don’t believe it’s a disease. They think it’s an affective disorder.

Louis Aronne: It’s a disorder of willpower. If you would just try hard enough, you would be able to lose weight. Or people tell us when it comes to these new medications, so how long does the patient have to take it? I mean, what happens after they lose that 22 and a half percent weight loss? Do they stop it? And then their brain has learned to eat less? And the answer is, what about diabetes medicine? When do you stop diabetes medicine?

Phil Stieg: And you think that that’s still prevalent in this day and age where there’s so much research now demonstrating that there’s hormonal and metabolic processes going on that exacerbate weight gain?

Louis Aronne: I know it’s prevalent because our patients will tell us that their doctor stopped the medicine or their doctor told them they didn’t need the medicine anymore because they got down to whatever weight they needed to get to. Why are you still taking that medicine? You lost the weight. We hear this all the time. –

Phil Stieg: So, now you’re this with this medication, you’re going to transform the management of obesity.

Louis Aronne: I believe that that’s true. What I believe is going to happen is that right now the treatment paradigm for many illnesses is to directly treat the complication of obesity, to treat the high blood pressure, the diabetes, the high cholesterol, and to ignore the patient’s weight, because you have medicines that work, and you’ve been trained how to do that. I think that we’re going to flip the whole thing over to treat the obesity first, because we will be able to treat it. And then if we can’t treat the high blood pressure and diabetes, then we have other agents that can work there.

Phil Stieg: Dr. Louis Aronne, a world’s expert on the diagnosis and treatment of obesity and obesity, thank you for enlightening us on the interaction between all of the neurons of the brain that affect how we eat and behave. It’s been a great pleasure having you on the show.

Louis Aronne: Thanks very much for having me, Phil

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