Insulin resistance, high cholesterol, fatty liver, greater risk for diabetes, heart disease, and stroke are all related to obesity, but are likely not caused by it, according to a review in Trends in Endocrinology and Metabolism.
In fact, 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 and, thanks to modern technology, we move far too little. Until that changes, there isn't any end in sight 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 Roger Unger, a researcher at the University of Texas Southwestern at Dallas. "Overnutrition used to be rare—reserved for those in the castle. Today, it's just the opposite. Bad calories are so cheap that anyone can afford to get overweight."
The authors say there is 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.
There is some disagreement in the field about whether insulin resistance is a primary cause of metabolic syndrome or just one of its features. But the authors say insulin resistance is likely a "passive byproduct" of fat deposition in the liver and muscle once storage in fat cells begins to fail.
It also makes sense that cells that have already taken on too much fat would begin to exclude glucose, causing its levels in blood and urine to rise. Once in cells, glucose becomes a substrate for the production of more fat. "The body is doing what we should have done—keep excess calories out—and it may be protective," says Unger.
At the center of the transition from protective obesity to metabolic syndrome is resistance to the fat hormone leptin, well known for its appetite-suppressing effects. The hormone is also responsible for partitioning fat in the body. The rise of leptin as fat stores grow is therefore an adaptive response, but that can only go so far before resistance sets in.
Based on the genes they carry, some people will be better able to sustain lipid storage in fat and can get away with being overweight, even obese, without the other symptoms. Eventually, though, the need to cut calories is something all of us will face.
"Once you reach a certain age, almost everybody is leptin resistant," Unger says. "Nature stops protecting you once you pass the reproductive years," requiring all of us to watch our diets and do exercise.
Citation: Roger H. Unger, Philipp E. Scherer, 'Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity', Trends in Endocrinology and Metabolism, March 2010; doi:10.1016/j.tem.2010.01.009
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