Obesity as protection against metabolic syndrome, not its cause

The collection of symptoms that is the metabolic syndromeinsulin resistance, high cholesterol, fatty liver, and a greater risk for diabetes, heart disease, and strokeare all related to obesity, but, according to a review in the March 9th issue of the Cell Press publication Trends in Endocrinology and Metabolism, not in the way you probably think they are.

In fact, says Roger Unger of the University of Texas Southwestern at Dallas, obesity is the body's way of storing lipids where they belong, in fat tissue, in an effort to protect our other organs from lipids' toxic effects. It's when the surplus of calories coming in gets to be too much for our fat tissue to handle that those lipids wind up in other places they shouldn't be, and the cascade of symptoms known as metabolic syndrome sets in.

It comes down to simple facts that all of us know on some level or another: Americans since the 1950s eat too much high-calorie food loaded with carbs and fat (what Unger calls "potent adipogenic nutrient mixtures") and, thanks to modern technology, we move far too little. Until that changes, Unger doesn't see any end to the growing epidemic of metabolic syndrome. Still, our metabolisms aren't broken; the pathways that squirrel fat away as an energy source for use in lean times are just completely overwhelmed. "We are pushing our homeostatic capability to the maximum," says Unger, who coined the term "lipotoxicity" in 1994. "Overnutrition used to be rarereserved for those in the castle. Today, it's just the opposite. Bad calories are so cheap that anyone can afford to get overweight."

Unger cites plenty of evidence in support of a protective role for obesity. Genetic manipulations in mice that increase or decrease fat formation have provided evidence that adipogenesis, meaning the generation of fat cells, delays other metabolic consequences of overeating. The reverse is also true, he writes. Obesity-resistant mice have in some cases been found to develop severe diabetes upon eating too much, as a result of lipid accumulation in tissues other than fat...