New Clues to Why We Gain Weight

Eric Ravussin holds the Douglas L. Gordon Chair in Diabetes and Metabolism at Pennington Biomedical Research Center in Baton Rouge, Louisiana. He is also chief of Pennington’s Division of Health and Performance Enhancement and heads Pennlngton’s Nutrition Obesity Research Center. He is a principal investigator in the CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) Study and a former president of the (U.S.) Obesity Society. From 1998 to 2000 he was director of endocrine research at the Lilly Research Laboratories of the pharmaceuti¬cal firm Eli Lilly and Company. Ravussin spoke by phone to Nutrition Action’s Bonnie Liebman from Baton Rouge.

We live surrounded by a 24-hour, all-you-can-eat buffet. And yet some people manage to stay lean while everyone else gains weight. Is it will power? Genes? Metabolism?

“Given the world we live in, the real question isn’t why people get fat, but why some people manage to stay thin,” says obesity researcher Eric Ravussin.

Here are some surprising new leads into what packs on the extra pounds... and how to keep them off.

Leptin
Q: What do we know about obesity that we didn’t know 20 years ago?

A: Since the discovery of leptin in 1994, we have made giant strides in understand¬ing how the body regulates fat stores. Lep¬tin is a hormone produced by fat cells. It tells the brain when the body has enough fat.

When people lose weight, their leptin goes way down, and the body interprets that as a state of starvation. In the leptin¬ deficient mouse, the response is “I need to eat. I don’t have any energy stores.” The same happens in people.

Q. So lower leptin levels push us to regain the lost weight?

A: Yes. Almost everyone can lose 10 per cent of their weight. It’s not easy. You have to eat less and exercise more. But 95 per cent of people can do it.

Unfortunately, 95 per cent of people regain at least some of the weight they lose.

Q: Why?

A: When people lose 10 to 20 per cent of their body weight, their metabolic rate drops. Their metabolism be¬ comes thrifty. So they need fewer calories to stay at their lower weight than people who have always weighed that much.

That puts the dieters at higher risk of regaining the lost weight. And they’re hungry most of the time. So it’s a constant struggle.

Q: And leptin is the culprit?

A: Yes. When researchers replenish diet¬ers’ leptin by injecting it, their metabolic rate goes back up. We naïvely thought that if you gave the overweight enough leptin, it would shut down their food intake and also increase their metabolic rate. But it doesn’t because most over¬weight people are resistant to leptin.

Q. Is that like insulin resistance?

A: Yes. Eighty to 90 per cent of people with type 2 diabetes continue to produce insulin, but the insulin doesn’t work because they are resistant to it.

We have found the same with people who are obese. Their bodies produce lep¬tin in abundance but the leptin doesn’t work. In fact, many people are resistant to both leptin and insulin.

Q: Is there any way to get around lep¬tin resistance?

A: Drug companies have looked, but it’s not that easy. And they haven’t just looked at leptin. For example, melanocor¬tin receptor 4 signals the body to stop eat¬ing. Scientists thought that if they could find a drug that would keep this receptor active, it would cause weight loss. And pharmaceutical companies developed the drugs, but they don’t work because the body has other ways to avoid starvation.

When the survival of an organism is at stake, the body has redundant systems. It’s like if a plane had only one system to take down the landing gear, you would be in big trouble if the hydraulic system didn’t work. So the body has redundant systems to avoid starving.

Genes & Epigenetics
Q: Do genes make some people fat?

A: Any population has a range of body weights. That’s mostly due to genes. The prevalence of obesity has been climbing steeply from the late 1970s to 2010. But people on the skinnier end of the range have remained skinnier and the heavier have gotten even heavier.

Some people are better at resisting weight gain than others. They’re re¬strained eaters or their genes help them resist weight gain.

Q: How?

A: Genes affect both energy intake and energy expenditure. For example, the metabolic rate of people of the same sex, age and body size may vary by as much as 500 calories per day.

Genes also affect how active we are when we’re not trying to exercise. Some people jiggle their legs, tap their fingers, and otherwise fidget more than others. They burn more calories unconsciously. One study estimated that if obese people spent about 2 3/4 hours more each day standing or walking instead of sitting, they could burn an extra 350 calories a day.

Leptin’s Legacy
Most of leptin’s effects occur through the hypothalamus, the part of the brain that integrates all basic drives and regulates food intake, energy expenditure, and glucose and fat metabolism. With weight loss, the body’s fat stores shrink and therefore produce less leptin. The hypothalamus responds by shifting several body systems into starvation mode. It results in urges to eat more and expend less energy, making it difficult to maintain the weight loss. Other changes, such as increased stress response and weakened reproductive and immune function, cause their own set of problems.

Q: Why would our genes set us up for obesity?

A: As humans evolved, people who could take in lots of calories when food was available and store those calories efficiently as body fat were the people most likely to survive through famines and to pass on their genes. For millions of years, evolution favoured people of this ‘thrifty’ genetic type.

Q: Now it’s a liability?

A: Yes. The environment has changed the whole picture because today we can eat very palatable food very cheaply all the time, and we don’t need to expend very much energy to get this food. Our genes haven’t changed over the last 40 years, but our environment has.

Q: And our environment promotes weight gain?

A: Yes. I worked for a long time with the Pima Indians in Arizona. More than 75 per cent of them are overweight or obese.

There is another community of Pimas in Mexico that has the same—or close— genetic pool, yet very few of them are overweight or obese. The rate of diabetes is 6 per cent in the Pimas in Mexico versus 45 per cent in the Pimas in Arizona. In dia¬betes, as with other diseases, genetics loads the gun and environment pulls the trigger.

If you bring these people from the Sierra Madre to southeast of Phoenix, it’s very likely that they’ll become like the Pimas in Arizona. It’s not like the Mexican Pimas are malnourished. They just have a healthier diet with more foods they get from the ground—more veg¬etables and fruit. And they have to burn more calories to get their food.

Q: Can anything change our genes?

A: No, but it may be possible to change how genes are turned on and off. At Pennington’s Nutrition Obesity Research Center, our focus is nutritional program¬ming. When you have an inbred strain of animals like mice, 99.9 per cent of their genes are the same. Yet when you place the mice on a high-fat diet, some gain more weight than others. And when you put them in cages where they can run in a wheel, there is a huge variability in how much they run. Despite having exactly the same genome, you see differences.

Q: And the same is true in people?

A: Yes. Ten years ago, if I had seen identi¬cal twins with an exact, 100 per cent match in DNA, I would have told you that they are exactly the same. Not any more. We see differences that go beyond DNA, and those differences seem to be partly due to the influences of nutrients during fetal and early life.

Studies of people born in the 1920s have found that having a low birth weight in¬creased their risk of cardiovascular disease, diabetes, and obesity. Something which is not genetic—but what scientists call epigenetic - happened to these babies.

Q: What does epigenetic mean?

A: Epigenetic literally means above genes.

Epigenetics changes the expression of genes. For example, if you have a gene that produces leptin, you can change the amount of leptin that is made. This is a fascinating area of research.

When it comes to obesity, we are 10 years behind cancer researchers, who have been dealing with epigenetics for more than 20 years.

Temperature
Q: What else might affect weight?

A: Last year, three studies reported the dis¬covery of brown adipose tissue—also called brown fat—in adults. White adipose tissue is where your body stores calories as fat. In contrast, brown adipose tissue burns as many calories as skeletal muscle. Instead of storing fat, brown adipose tissue burns it.

We believed for 20 years that brown adi¬pose tissue was present only in newborns. It’s a cold shock for babies to be born. After being in the womb at 37 degrees, they need to maintain their temperature going into a room that’s at 20 degrees. So they need to generate a lot of heat, and it’s generated by brown adipose tissue.

Q: And researchers thought that brown adipose tissue disappeared?

A: Yes, we thought it was gone after the first two years of life. But scientists who were using PET scans to look for tumours, which show up because they consume a lot of glucose, found healthy areas that also consume more glucose. The researchers did biopsies and found that it was brown adipose tissue.

Now there’s hope that people may be able to increase their mass of brown adi¬pose tissue. The heavier you are, the less you have. It decreases with age and it’s surprisingly higher in females.

Q: How can people increase their brown adipose tissue?

A: That’s what we’re studying. One way is to increase cold exposure, but that’s not easy because everything now is kept at a comfortable temperature. People used to burn more calories staying warm when it was cold. When it was hot outside, the heat curbed our appetites. Now we keep our thermostats set at about 20 degrees whether it’s cold or hot outside.

Viruses
Q. Could a virus cause weight gain?

A: Scientists are looking at about 10 different viruses that may contribute to obesity. The researcher doing much of the work on adenovirus-36, for example, is two doors down from me.

Human adenovirus-36 increases fat stores in chickens, mice, and non-human primates. Infected marmosets gained four times more weight than uninfected con¬trols. We can’t give the virus to humans to see if they gain weight, but in one study of roughly 500 people, researchers found antibodies to the virus in 30 per cent of the obese but in only 11 per cent of the non-obese. That means a greater percentage of the obese had been infected with the virus.

On the other hand, it’s not like cholera. I don’t think we have an obesity epidemic because of a virus. But we have been a little naïve to say that only food intake and exercise matter.

Gut Bacteria
Q: What else might matter?

A: The bacteria in your gut are very important. Several years ago, researchers showed that by transplanting feces from a fat animal to a lean animal, you can make the lean one fatter, and by transplanting feces from a lean animal to a fat animal, you can make the fat animal leaner.

And in early October, at the European Congress on Diabetes, there was a report showing that a human-to-human feces trans¬plant could make someone less insulin resistant. You have to take antibiotics to get rid of your gut bacteria before the transplant— and I don’t know how it’s done— but they found that transplanting feces into people at risk for the metabolic syndrome improved their insulin sensitivity.

Q: Does our diet influence our gut bacteria?

A: Yes. The Pima Indians in Mexico have an enormous amount of fibre in their diet—10 times more than the Pimas in Arizona, who have much higher rates of diabetes and obesity. The Mexican Pimas eat a lot of beans, which have a lot of resistant [indigestible] starch. So they have more fermentation in the lower gut, which changes their bacteria. But we don’t know yet if eating beans or anything else would help people lose—or not gain—weight.

Surgery
Q: What else has surprised you?

A: One of the fascinating stories is the success of surgery for obesity, especially surgery that bypasses part of the small intestine.

We know that the surgery reduces the volume of the gut, and that it changes the delivery of nutrients to the gut. But when surgery changes the tubing of the gut, so that food totally skips the duodenum, these people are not as hungry.

Q: And it‘s not just because their stomachs are smaller?

A: No. So now there are companies mak¬ing sleeves that can be put into the gut so food avoids contact with the duodenum.

Why would that help? It’s because so many peptides—protein fragments—are secreted by the cells in the gut. Glucagon¬-like peptide-1 is the major one. It stimu¬lates insulin secretion. If you change the secretion of these peptides, it makes people less hungry.

Q: Does it also change their response to insulin?

A: Yes. Patients lose their insulin resistance. I recently went to Rome to attend the first meeting on using surgery to treat type 2 diabetes. It was basically gastric bypass surgery, which can cure people of type 2 diabetes. And it’s not just because they’re losing weight.

The Bottom Line
Q: What can people do today?

A: I think we have too much snacking. People basically take in calories all the time. That’s not a good thing.

And studies by Barbara Rolls at Penn State show that the volume of the food you eat is very important. If you have lower calorie density, you can eat the same volume with fewer calories. [See “Perfecting Pasta.”]

We know that those who engage in more physical activity are more likely to maintain their weight loss. I’m skinny but I love to eat. The reason I exercise is to be able to eat what I want.

Q: How can we reverse the obesity epidemic?

A: First, if it’s an epidemic, that means it’s been triggered by the environment. And what do you do if you have too much malaria? You drain the swamps. What do you do if you have too many deaths on the highway? You impose seat belts. These are public health measures.

What do you do when you have an epidemic of obesity? We’re going to have to impose taxes on soft drinks and subsidize healthier food. And we need safe neighbourhoods where kids can play.

Where I grew up in Lausanne, Switzerland, physical education was mandatory. We didn’t have the elite high school teams where if you’re not on the varsity, you don’t do anything.

My grandmother knew that if you want to lose weight, you have to eat less and exercise more. We’re still there, but the real trig¬ger of the obesity epidemic is the environment.

Perfecting Pasta - How to Lower Calorie Density
• Decrease the amount of pasta
• Increase the amount of vegetables
• Omit the cream sauce

More food, fewer calories. You can feel full on fewer calories by cutting a dish’s calorie density. Replacing the fatty cream sauce and some pasta with vegetables slims down this pasta primavera.

Source: The Volumetrics Eating Plan by Barbara Rolls and Robert Barnett (2000, HarperCollins).

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