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How and Where Fat is Stored Predicts Disease Risk Better than Weight

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A new study in mice indicates that overeating, rather than the obesity it causes, is the trigger for developing metabolic syndrome, a collection of heath risk factors that increases an individual’s chances of developing insulin resistance, fatty liver, heart disease and type 2 diabetes.

How and where the body stores excess, unused calories appears to matter most when determining a person’s risk of developing metabolic syndrome, researchers at UT Southwestern Medical Center suggest.

“Most people today think that obesity itself causes metabolic syndrome,” said Dr. Roger Unger, professor of internal medicine at UT Southwestern and senior author of the study. “We’re ingrained to think obesity is the cause of all health problems, when in fact it is the spillover of fat into organs other than fat cells that damages these organs, such as the heart and the liver. Depositing fatty molecules in fat cells where they belong actually delays that harmful spillover.”

The study, available online, is to be published in a future issue of the Proceedings of the National Academy of Sciences. It is among the first to suggest that weight gain is an early symptom of pre-metabolic syndrome, rather than a direct cause.

“Obesity delays the onset of metabolic syndrome, but it doesn’t prevent it,” said Dr. Unger, who has investigated diabetes, obesity and insulin resistance for more than 50 years. “People who are obese or overweight are on the road to developing metabolic syndrome unless they stop overeating. Sooner or later, it will happen.”

Currently about 50 million Americans suffer from metabolic syndrome. The exact cause of metabolic syndrome is unknown, but obesity and lack of exercise have been considered to be the primary underlying contributors to its development. Several studies in Dallas have shown that overweight patients with metabolic syndrome have increased fat levels in their liver, heart and pancreas.

Individuals with congenital generalized lipodystrophy – a genetic condition in which people are born with no fat cells in which to store fat – develop metabolic syndrome at an earlier age than people who are obese. They also develop more severe cases of metabolic syndrome earlier than their obese counterparts.

The goal of this study was to determine whether an individual’s capacity to store fat in fat cells plays a role in whether they develop metabolic syndrome and type 2 diabetes and at what point that occurs.