Washington University. US: New
research 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.
In a study at Washington University School of Medicine
in St. Louis, 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 findings are published Jan. 2 in The Journal of Clinical Investigation.
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 percent of his or her body
weight,” said
first author Elisa Fabbrini, MD, PhD, 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 dietitian. 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
Samuel Klein, MD, the Danforth Professor of Medicine and Nutritional
Science and director of Washington University’s Center for Human
Nutrition.
“This observation is important clinically because about 25 percent 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, who also
directs the Division of Geriatrics and Nutritional Science and the
Atkins Center of Excellence in Obesity Medicine.
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?”
As they look for answers, Klein and his colleagues plan to more
closely analyze fat, muscle and liver tissue and to include lean people
in future studies so that the researchers can learn more about how and
why some individuals are protected from metabolic problems while others
are vulnerable.
Editor’s note: While the study was underway, it was featured in the HBO documentary “Weight of the Nation.”