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Scientists Extend Search for an Obesity Breakthrough

Obesity AAAS S&T Policy Fellows Forum


Experts bring diverse approaches in fight to reverse obesity epidemic. From left, Lex Kravitz; Lita Proctor; R. Nisha Aurora; and Monica Skarulis.  |  Juan David Romero/AAAS

A key brain region no bigger than the tip of your thumb, exercise habits, bedtimes, and shift work represent a sliver of the research areas scientists are tackling in their battle to reverse the global epidemic of obesity, a meeting of experts at AAAS’ Washington, D.C. headquarters revealed.

Speakers unpacked what drives obesity and how to stop it during a 30 June symposium organized by several AAAS Science & Technology Policy Fellowships affinity groups.

Obesity is a global epidemic that requires summoning multiple disciplines, from biology and behavioral sciences to economic analysis and public policy, panelists said. Since 1980, the rate of obesity has nearly doubled worldwide, according to a 2011 study published in The Lancet.

The U.S. Centers for Disease Control and Prevention (CDC) estimated the medical cost of obesity in the United States to be $147 billion in 2008, a price tag that is growing. In the United States, more than 78.6 million adults aged 18 and older are obese, according a 2014 report in the Journal of the American Medical Association.

Monica Skarulis, M.D., chief of the clinical endocrinology section in the diabetes, endocrinology and obesity branch of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), zeroed in on the brain’s complex circuitry that drives what people eat and how quickly they burn it up.

The brain’s hypothalamus, despite weighing the same as a nickel, plays an outsized role in the production of hormones that flip on and off other hormones to regulate eating behavior as well as other functions vital to life, Skarulis explained.

“We live in a toxic food environment and it’s more than just a rhetorical question to ask: Do we eat to live, or do we live to eat?” Skarulis said. Still, she added, the better question animating scientific studies is which force plays a bigger role in feeding the obesity epidemic: the physiological system that controls body weight, or neurological forces that spike appetite and longing for food?

Lex Kravitz, a NIDDK neurologist who studies a chemical in the brain, dopamine, that helps control the brain’s reward and pleasure centers, has taken on one part of that query. He found exercise by itself results in only minimal weight loss in humans, despite the multiple health benefits it confers, a fact that is well understood among researchers, he said, but not as well communicated to the public.

More studies are needed to understand why obese people are less apt to engage in physical activity, he said. Research that examines what is going on at the cellular and molecular level is particularly necessary, Kravitz added.

In another area, R. Nisha Aurora, M.D., an assistant professor of medicine at Johns Hopkins University School of Medicine, walked through studies that have found a link between insufficient sleep and obesity in adults and children.

School-age children need at least 10 hours of sleep daily, teens at least nine hours to 10 hours, and adults at least seven hours to eight hours, according to the National Heart, Blood and Lung Institute. The CDC has found about 35% of Americans report getting fewer than seven hours of sleep.

Shift workers, defined as those who work outside of the regular daytime band of 7 a.m. to 6 p.m. and account for about 20% of the workforce in each industrialized nation, are particularly susceptible to obesity, Aurora said, recommending that policymakers take steps to reduce such schedules.

Skarulis said federal researchers are particularly focused on how to better understand and reverse the ferocity of the body’s defense system that thwarts weight loss, a reaction that was vividly displayed by the results of a well-publicized, if disheartening, study conducted by one of her colleagues at NIDDK.

In the study, Kevin Hall followed up six years later with a group of obese contestants who appeared on Season 8 of NBC’s reality television show “The Biggest Loser” to study what happened to the contestants who dropped dramatic amounts of weight.

In particular, Hall wanted to know if the contestants, who had exercised vigorously and preserved most of their muscle tissue even as they shed fat, were protected from the perverse reaction set off after weight loss: The body reprograms hormones such as the appetite-controlling Leptin and Ghrelin, and downshifts the body’s metabolic meter to slow the rate at which calories burn – its natural defense against the loss of body weight.

Hall found the contestants were not immune. Not only were their metabolic rates reset downward, their newly set metabolic rates were even more sluggish than they had been before weight loss, and the new set point was locked in even after the contestants regained weight. 

“This is a very sobering thing, very disturbing,” Skarulis said. “It’s caused a lot of controversy.”

In response, federal scientists are looking for ways to highjack the body’s systems to intercept signals the brain’s circuitry receives from the gut, fat, other organs, and intestinal microbes. They want to harness the weight regulation system and amp up sluggish metabolic rates, an outcome that will not just help reduce weight, but will take on the biggest challenge of all: keeping lost weight off.

Bariatric surgery, a procedure that reduces the volume of food the stomach can hold, has been “very effective,” and shown to cure diabetes, Skarulis said. Among other higher risk factors for disease that obese people face are heart disease, stroke, type 2-diabetes, and some cancers, according to the CDC. 

Promising drugs are also in the works, she said, pointing to early clinical studies of one drug that decreases food intake, increases by 7% the amount of calories the body burns, and boosts the production of hormones that make people feel full.

“In the last five years there has been a tremendous increase in the tools we have to fight this epidemic,” Skarulis said.