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Obesity not always linked to metabolic change

Research at Washington University School of Medicine in St Louis demonstrates that obesity does not always go hand in hand with metabolic changes in the body that can lead to diabetes, heart disease and stroke.

Researchers found that a subset of obese people do not have common metabolic abnormalities associated with obesity, such as insulin resistance, abnormal blood lipids (high triglycerides and low HDL cholesterol), high blood pressure and excess liver fat.

In addition, obese people who didn’t have these metabolic problems when the study began did not develop them even after they gained more weight.

The study involved 20 obese participants who were asked to gain about 15 pounds over several months to determine how the extra pounds affected their metabolic functions.

"Our goal was to have research participants consume 1,000 extra calories every day until each gained 6% of his or her body weight," said first author Dr Elisa Fabbrini, assistant professor of medicine. "This was not easy to do. It is just as difficult to get people to gain weight as it is to get them to lose weight.

All of the subjects gained weight by eating at fast-food restaurants, under the supervision of a dietician. The researchers chose fast-food chain restaurants that provide rigorously regulated portion sizes and nutritional information.

Before and after weight gain, the researchers carefully evaluated each study subject's body composition, insulin sensitivity and ability to regulate blood sugar, liver fat and other measures of metabolic health.
After gaining weight, the metabolic profiles of obese subjects remained normal if they were in the normal range when the study began. But the metabolic profiles significantly worsened after weight gain in obese subjects whose metabolic profiles already were abnormal when the study got underway.

"This research demonstrates that some obese people are protected from the adverse metabolic effects of moderate weight gain, whereas others are predisposed to develop these problems," said senior investigator Dr Samuel Klein, the Danforth professor of medicine and nutritional science and director of Washington University’s Centre for Human Nutrition.

"This observation is important clinically because about 25% of obese people do not have metabolic complications," he added. "Our data shows that these people remain metabolically normal even after they gain additional weight."

As part of the study, the researchers then helped the subjects lose the weight they had gained.
"It's important to point out that once the study was completed, we enrolled all subjects in our weight-loss program to make sure they lost all of the weight they had gained, or more," said Klein.

The researchers identified some key measurements that distinguished metabolically normal obese subjects from those with problems. One was the presence of fat inside the liver. Those with abnormal metabolism accumulated fat there.

Another difference involved gene function in fat tissue. People with normal metabolism in spite of their obesity expressed more genes that regulate fat production and accumulation. And the activity of those genes increased even more when the metabolically normal people gained weight. That wasn't true for people with abnormal metabolism.

"These results suggest that the ability of body fat to expand and increase in a healthy way may protect some people from the metabolic problems associated with obesity and weight gain," said Klein.

He noted that obesity contributes to more than 60 different unhealthy conditions.

"We need more studies to try to understand why obesity causes specific diseases in some people but not in others," Klein said. "Could it be genetics, specific dietary intake, physical lifestyle, emotional health or even the microbes that live in the gut?"

[link url="http://www.sciencenewsline.com/articles/2015010622430081.html"]Full Science Newsline report[/link]
[link url="http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00553-1"]Cell Metabolism article summary[/link]
[link url="https://news.wustl.edu/news/Pages/27823.aspx"]Washington School of Medicine release[/link]
[link url="http://www.jci.org/articles/view/78425"]Journal of Clinical Investigation article[/link]

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