Last year, Harvard University sent Peter Ferket mouse poo to light on fire. A professor of poultry science at North Carolina State University, Ferket began by adding flammable flour dust to his samples. He then put the mixture into a sealed, stainless steel cylinder filled with pure oxygen, surrounded the cylinder with a couple liters of water, and lit its contents on fire with an electrical filament. The high temperature and pressure of the combustion left only a little mineral-laden ash, and slightly warmed the surrounding water bath. Although the samples were minute, their scientific output was substantial: The study suggested that two mice can eat and excrete the same amounts, but one can end up obese.

If the same results hold for people, it may change how we see one of the most important health issues in the Western world. If, even some of the time, obesity is not due to a person overeating or under-exercising, should discrimination against the obese carry the same legal consequences as discrimination based on age, race, or gender? And by the same measure, should purveyors of fattening foods be made unaccountable for the perceived consequences of their products?

Ferket became interested in exploding manure to explore a rather more prosaic challenge: developing better chicken feed. Good food contains more condensed energy, he reasoned, so more of its caloric content would be absorbed by the chicken, and less excreted. To see how much is excreted, he measures the energy released by burning the manure, in a technique called bomb calorimetry. Word of Ferket’s expertise eventually reached several researchers at Harvard, who had a different kind of problem.

They were studying mice that had been made obese with the deletion gene called Mrap2. As pups, the altered mice ate the same amount as normal mice, but quickly became severely obese. Only when they were fed 10 to 15 percent less did they slim down to the size of their unaltered siblings. “That puzzled us,” says Joseph Majzoub, an endocrinologist at Harvard and senior author of the study published in a July issue of Science.1 “Most forms of obesity,” he explains, “have almost always been associated with easily detectable increases in eating behavior at a young age.”

At first, the researchers thought the obese animals must be moving less. To test this hypothesis, they put the mice in a sensor-laden enclosure that measured their activity level, how much oxygen they breathed, and how much carbon dioxide they exhaled. But this measurement only deepened the puzzle. “Surprisingly, we found that animals were not burning less energy either,” Majzoub says.

This was strange. The animals weren’t eating more, and they weren’t burning less. Perhaps, the researchers thought, the obese mice were somehow gleaning more calories from each mouthful and turning those calories into fat, while normal mice pooped them out. They needed an expert in bomb calorimetry, so they asked Ferket if he could work his magic. “Sure,” Ferket said, “send me some mouse turds.”

Six weeks after Majzoub mailed his samples to Ferket, he received some unexpected results. The energy content of feces from the obese mice was the same as the content from the normal mice fed the same diet, meaning that the same number of calories were being absorbed in the intestines. Becoming obese takes a lot of energy, but the obese mice didn’t seem to be getting extra energy, or saving any. “The first law of thermodynamics requires that energy be balanced,” says Majzoub, “and I am not willing to throw that out the window.”

This was strange. The animals weren’t eating more, and they weren’t burning less.

How exactly obesity occurs without excess calorie intake or decreased output remains unclear. Mrap2 is expressed primarily in the brain, in a region that regulates metabolism, the process by which an organism converts food into energy for life-sustaining processes. Perhaps, says Majzoub, the obese mice metabolize calories differently, turning the same calories into fat that normal mice convert into building proteins, or use in other internal tasks. Mice, like humans, do not consciously control their metabolism.

A similar mechanism could be tied up with some instances of human obesity. The study also found that mutations in the human version of MRAP2, though rare, link to severe early-onset obesity in people. Majzoub predicts that other, yet to be found mutations in MRAP2 and additional genes linked to human obesity might help explain why some people cannot seem to maintain an average weight no matter their food intake.

Currently, United States federal law does not protect people against obesity discrimination. Unlike gender, race, or age, obesity is perceived to be something that a person can alter with enough willpower, says Rebecca Puhl, director of the Rudd Center for Food Policy & Obesity at Yale University. As a result, court cases centered on obesity involve plaintiffs claiming that their weight represents a disability. Because “there are no specific laws that cover weight discrimination, people have had to pursue cases under things like the Americans with Disabilities Act [ADA],” Puhl says. However, she says the plaintiffs often lose. For example, in 2002, a truck driver filed a case against his employer claiming that he had been fired for a disability—his weight. The judge disagreed, ruling that his obesity was not a disability because his weight was not a symptom of a disease. In 2006, the U.S. court of appeals upheld the ruling, stating, “…we hold that to constitute an ADA impairment, a person’s obesity, even morbid obesity, must be the result of a physiological condition.”

Yet Majzoub’s study on mice suggests that obesity may in fact be controlled by the unalterable way an individual’s body functions. Food sellers, too, would be off the hook. In 2004, the “Cheeseburger Bill,” which banned lawsuits against food manufacturers for an individual’s obesity, was passed in the U.S. House of Representatives, but not the Senate. In 2005, the bill was reintroduced by Florida Congressman Ric Keller. In that election period, Keller was one of the top recipients of McDonalds’ and Burger King’s donations to individuals in the House. Still, it faltered in the Senate again. Fast food companies remain liable today—but if a physiological conception of obesity might give the Cheeseburger Bill new life.

The understanding of obesity’s origins is far from complete. The Mrap2 gene has only been linked to human obesity in rare cases, and obesity may very well result from a mix of genetic and other factors, ranging from overeating, to stress levels, to gut microbes. Yet, the Harvard mouse study suggests that society should withhold their judgments against overweight people. “Many of us unfortunately have had an attitude towards obese people [in that we see them as] having a lack of willpower or self control,” he says. “It’s clearly something beyond that.”





Jenny Morber is a freelance science writer based in Fairfax, Virginia.







References

1. Asai, M., et al. Science 341(6413), 275-278 (2013).