The Science of Fat


More than one in three American adults is considered obese. Georgia State’s new Center for Obesity Reversal is tackling the epidemic by investigating what might be making us fat: our brains

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“Introducing Diet Coke” was the commercial jingle in everyone’s head that announced the zero-calorie soft drink’s arrival on the market. And fitness celebrity Richard Simmons hosted a top-rated talk show. Fitness was in fashion, but Americans just kept getting fatter. In the 1980s, Americans underwent their greatest weight gain in recorded history. And we haven’t taken the weight off since.

For 20 years, from 1960 to 1980, the nation’s obesity rate held steady at 13 to 15 percent of the adult population, according to the Centers for Disease Control. But from 1980 to 1988, nearly 10 percent more American adults became obese to include 23 percent of the population. Ten more years added another nearly 10 percent. In 1999, 30 percent of American adults were obese. And the number has steadily risen since then. Today, more than one in three Americans over age 20 is obese. The weight-loss industry is valued at $20 billion. And 108 million Americans are on a diet at any given time.


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Because diet and exercise just aren’t enough, says Timothy Bartness, Regents’ Professor of Biology and director of Georgia State University’s new Center for Obesity Reversal.

“Eat less and exercise more,” Bartness said. “If you’re going to lose weight, that has to happen. That’s the tried and true. But the tried and true thing simply hasn’t worked.”

Bartness doesn’t seek an alternative to diet and exercise, but rather, a way to trigger the biological processes that would boost the efficacy of diet and exercise. The Center for Obesity Reversal will conduct research that explores these processes. Days before the center became a university research center in June, Bartness won a $2.5 million renewal of the MERIT award from the National Institute of Diabetes and Digestive and Kidney Diseases to study how the body breaks down fat.

“The idea here at the center is to try to identify these underlying mechanisms that promote the reversal of obesity when we exercise more and eat less, and the mechanisms that impede obesity reversal,” Bartness said.

He hopes the research will reveal ways we can trick the brain and shut off those systems that cause the body to cling so tightly to fat.

 

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Survival of the fittest. It’s the key principle of biology, and it governs the life course of all living things. For humans, this means the body does what it must to stay strong enough to reproduce and carry on the species. When you take action to lose weight — by cutting calories and increasing exercise — your brain gets the message you’re wasting away and does what it must to hold onto weight.

“If you don’t have energy, you don’t reproduce,” Bartness said. “So if you try to lose weight, your metabolism decreases. If you affect one system that’s involved in body weight, another one will just kick in to compensate for it.”

Simply put, losing weight through diet and exercise alone is really hard. A man who eats 3,200 calories a day would have to run a marathon to burn it off. That’s 26.2 miles. At that rate, a 30-minute go on the treadmill wouldn’t even burn off a meal. And the uphill battle doesn’t end when all the weight comes off. Studies show that in order to maintain weight loss, an obese person who becomes thin has to take in 25 to 30 percent fewer calories for the rest of his or her life than someone of the same weight who has always been thin.

Bartness’s work focuses on how the brain gets the message you’ve begun to lose weight, and how it sends the body the message to hold onto weight. And, perhaps more important, how can science be used to manipulate that message?

“If the brain thought that you were fat, but you were really thin, then it wouldn’t engage these other compensatory systems to try to make you fat again,” Bartness said. “So maybe we could trick the brain.”

 

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The brain gets the message as to whether the body has enough fat stored to carry out the strenuous requirements of reproduction, such as puberty, pregnancy and lactation, through the hormone leptin, which was discovered in 1994, Bartness said. Fat cells release leptin in proportion to the amount of fat stored in these cells. The more fat in the body, the more leptin. When you start to lose fat through diet and exercise, leptin levels drop. When the brain catches wind of this, it activates responses that help hold onto remaining fat. But how did the brain get the message the body was losing fat?

Until recently, experts believed the brain took stock of body fat by monitoring leptin levels in the bloodstream. Though this is one way, leptin in the blood stream doesn’t reveal information about fat distribution. Leptin is evenly distributed throughout the body, but fat is not. And fat’s location in the body makes a difference. Fat in the trunk around the organs is a risk factor for many chronic diseases, while excess fat on the hips or thighs, for example, is not. Bartness’s lab recently found a path by which the brain gets the message as to fat’s location. When his team injected leptin directly into the fat of hamsters, the sensory nerves in that particular fat deposit were activated.

“Because the sensory nerves start firing, this means that they’re active,” Bartness said. “They’re sensing something. They’re telling the brain something.”

Years before this experiment, it was Bartness who helped convince the obesity research community of the sensory nervous system’s role in the regulation of body fat in the first place. The sensory nervous system is the part of the nervous system that conveys messages from the body to the brain, such as sensory nerves in the fingers that send the sensation of heat, cold or pain to the brain.

In the 1980s, when Jane Fonda and Richard Simmons were trying to help Americans shed all those extra pounds, Bartness was engrossed in seemingly esoteric research he thought had nothing to do with weight loss. He wanted to know how animals whose bodies respond to the seasons know what time of year it is. Take Siberian hamsters. The not-always-tiny creatures are naturally obese in the summertime, making them strong enough for reproduction at the perfect time of year to start a family in Siberia, when the weather is warm and fresh food abounds. They also have a brown coat in summer that camouflages them from the eyes of predators. When winter hits, the hamsters turn white to blend in with the snow. They sleep most of the day, while their bodies burn off much of the extra weight they carried all summer, and they don’t reproduce. When summer comes again, the process starts over.

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But what told their bodies to set all these advantageous processes into motion in order to ensure their species would reproduce and thrive?

Textbooks at the time suggested that epinephrine, a hormone secreted into the bloodstream by the adrenal gland, regulated fat loss in all animals, including humans. But Bartness didn’t believe this was possible because, like leptin, a hormone in the bloodstream would regulate fat equally throughout the body.

Bartness knew melatonin levels in the body increase at night, and because nights are long during a Siberian winter, he hypothesized that melatonin alerted the brain to the changing seasons and triggered the nerves in individual fat locations.

To test the hypothesis, Bartness and his colleagues shut down the nerves on one side of the body in a group of Siberian hamsters. When the days got shorter and the hamsters began to take on their wintertime appearances and behaviors, they only lost fat where their nerves were functioning, but not where they had been disabled.

Confirming the concept, Bartness found melatonin receptors in brain cells involved in the sympathetic nerves connected to the fat. Melatonin receptors are sites in the brain that respond to the presence of melatonin. During the long nights of winter, melatonin is present for longer periods at these receptors and triggers the break down of body fat in the areas where the corresponding nerves are located.

Bartness only wanted to know how the body knows it’s wintertime. But then the obesity crisis hit. And Bartness thought these hamsters might hold useful information.

“The idea was that they naturally go from a fat state to a thin state in an effortless way,” Bartness said, “but for us to lose weight, it’s very effortful. So if we could understand how they can go from fat to thin effortlessly, maybe we could make our way a little easier, too.”

Much research in the years following Bartness’s experiment has found that in fact the nervous system triggers fat loss in all mammals, not just Siberian hamsters.

“So it turned out to be a real basic, fundamental, biological property,” he said.

 

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While the nervous system tells the brain to hold onto fat or let it go, the brain may be simultaneously setting us up to keep feeding our fat, too.

“You and I forage for food in the grocery store and we hoard food,” Bartness said.

He notes the trends towards buying in bulk and stocking second refrigerators and freezers in our homes. Over time, as we’ve gotten bigger, so have our refrigerators. Bartness believes as our bodies acquire more fat, our brains are triggering behaviors to keep it there.

“It’s been studied now. Obese people bring home more food than thin people,” Bartness said. “Because if there’s not ice cream in the house, you probably won’t go out and get it. So we try to always make sure we have more ice cream than we need.”

Bartness doesn’t chalk this up to simple love of ice cream. He suspects there are concrete processes in the brain that make heavier people stock up on more food. Studies have shown the food-hoarding habits of overweight people are similar to those of people who are voluntarily fasting.

In experiments with hamsters, Bartness found that after a brief period of food deprivation, hamsters hoard more food rather than eat more food. When humans, as well as lab rats and Siberian hamsters, fast for a couple of days, their stomachs secrete a hormone called grehlin. Knowing this, in a later experiment, Bartness injected grehlin into hamsters that had just been fed. Though they were not hungry, the hamsters began to hoard food as if they had been starved.

If an animal’s hoarding instinct can be turned on, couldn’t it be turned off, Bartness wondered.

“If you could figure out the systems that are involved in hoarding,” he said, “then maybe you could stop animals — including us — from bringing home more food and storing it.”

 

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Even if Bartness has begun to crack the code behind the yo-yoing waistlines of Siberian hamsters, what does that have to do with us?

As what’s called a basic scientist, Bartness is part of the first step in answering that question. Basic scientists perform experiments – on rodents and other non-human subjects — to discover the concepts that lay the foundation for future human applications.

His Center for Obesity Reversal is taking a multipronged approach to identifying any and all of the biological processes that help keep us fat.

“When we start to lose weight, all of our physiology works against it,” he said.

The aim is that potential human applications of the research would come at the problem from all angles.

Researchers at the center are working to uncover all of those angles through exploring obesity’s relationship with breast cancer risk, diabetes, and memory among other topics. When it’s time to translate research findings into potential human applications, the Center for Obesity Reversal will call on its state and local partners at Emory University School of Medicine, Morehouse School of Medicine, Medical College of Georgia at Georgia Regents University and the Centers for Disease Control and Prevention.

The center’s work could lay the groundwork for medical treatments that will one day kick-start our diet and exercise routines. But Bartness isn’t going to put today’s Jane Fondas, people like Jillian Michaels, out of business.

“Exercise is great,” he said. “It will always be great. For stress reduction, for putting off heart disease, for blood sugar control, blood pressure control. It’s crucial for reducing disease risk in people who are overweight and obese.”

 Sonya Collins is an Atlanta-based independent journalist who covers health, health policy and scientific research. She is a regular contributor to WebMD Magazine, Pharmacy Today, Yale Medicine and Georgia Health News

Photo by Ryan Hayslip

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