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Does This Make Me Fat, Or Is It My Genes?

— A pair of married Harvard docs debate the causes of the obesity epidemic

MedpageToday

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BOSTON -- Picking a fight with your spouse is like scratching a scab -- it's rarely a good idea, and it's worse when done in public.

But that didn't stop one couple from getting into an argument during a session at the American Diabetes Association annual meeting. People within earshot of the couple, glasses of Chianti and Pinot grigio in hand, listened closely as the husband laid out the terms of the argument.

Far from being uncomfortable, the crowd seemed to be enjoying the face-off -- and they were getting CME credits too.

Who were the so-called opponents? -- the dean of the faculty of medicine at Harvard University in Boston, and his wife, , a professor of medicine at Harvard. Their topic was the root cause of the obesity epidemic.

While Flier made the case that obesity is largely because of genetics, Maratos-Flier posited that we should understand obesity in terms of its external circumstances.

The Environmental Argument

There is an obesity epidemic, there is no debate about that, with more than qualifying as obese, according to the CDC, and that costs healthcare billions of dollars each year. Worldwide, there are more than a billion obese people.

"But this is not an epidemic that is based entirely on french fries and burgers," said Maratos-Flier, pointing out that the U.S. is not the only country with an obesity problem.

Mexico, Australia, and the U.K. are in the same situation, as are other countries, despite varying dietary habits. There are many underlying risk factors for obesity -- poverty, race, education, and maternal obesity.

But there's another reason for the obesity increase, according to Maratos-Flier -- the availability of inexpensive, often nutritionally deficient food.

Food in the U.S. has stayed relatively inexpensive compared with the cost of other consumables. "If something is cheaper, it's easier to eat more of it, though we can't show causation," she said.

Obesity is hardly a modern disease, but one that's been around for ages, she pointed out, showing portraits of several figures in Tudor England.

At age 55, was believed to weigh more than 320 lbs. He reportedly consumed 5,000 calories a day and 70 pints of ale a week. His contemporaries weren't exactly skinny either, she said.

"Obesity was actually in vogue at the time," she said. "The right kind of environment will drive obesity in a major way."

Then there's the bad dietary advice based on biases, not data, that people follow. Type 2 diabetes patients were often told that 45% to 65% of their calories should come from starchy carbohydrates, but that only made sense in the era before people took insulin, she said.

Maratos-Flier counseled that we need to do away with the following beliefs:

  • One diet fits all populations
  • Breakfast is necessarily the most important meal of the day
  • Carbohydrates can "jump-start" the metabolism
  • Fats are less filling than other foods

She noted that an increasingly sedentary lifestyle is also an environmental factor in the rise of obesity. As jobs decline in the agricultural, building, and service sectors, daily routines have become more sedentary, she added.

The Case for Nature

Flier seemingly conceded the debate at the start of his argument. "I would be happy to declare her the winner of the debate right now," he said.

However, he noted that obesity and body mass index (BMI) is about 50% to 70% genetic. The evidence for this comes from three major sources: family studies of obesity, twin studies, and adoption studies.

In the twin studies, researchers would overfeed one twin and underfeed the other, but found that genetics accounted for some response, regardless of environment. Research has also been done on genes and obesity in mouse models.

Some genes were found to be strongly associated with obesity, but they are relatively rare, affecting only a small portion of those who are obese, Flier said. There are about 130 proposed genes that account for obesity, but only about 10 have been established in large studies and meta-analyses.

"Although obesity is clearly heritable, only a few genes were firmly associated with obesity or related traits," Flier said. In the last 10 years, genome-wide association studies have identified more than 75 new "obesity-susceptibility loci." These loci affect adult and childhood BMI, but not birth weight, and have a very low predictive value, he stated.

Research is still needed to identify the underlying genes and gain a better understanding of the role of epigenetic factors, Flier said. In addition, it seems that changes in intestinal bacteria have metabolic consequences, but most of the genes in the microbiome remain unidentified.

It's unclear how much environment and dietary factors affect the microbiome and exactly how changes in the gut affect obesity. In addition, research is needed on how the brain regulates appetite and satiety.

Flier stressed that there is so still much about obesity that remains a mystery. "Most of the answers right now are unknown," he noted.