Metabolic syndrome -- don't blame the belly fat

n both insulin resistant and insulin sensitive human subjects.

The subjects for the study were all young, lean, non-smoking, healthy individuals who were sedentary and matched for physical activity. Aside from insulin resistance in one cohort, these volunteers had none of the other confounding factors typically associated with obesity and type 2 diabetes, which have been thought to play a key role in the pathogenesis of the metabolic syndrome.

"Our hypothesis was that the metabolic syndrome is really a problem with how we store energy from food, Shulman explained. "The idea is that insulin resistance in muscle changes the pattern of energy storage."

After providing the study's subjects with two meals high in carbohydrates, Shulman and his colleagues turned to magnetic resonance spectroscopy to measure the production of liver and muscle triglyceride, the storage form of fat, and of glycogen, the storage form of carbohydrate. "What we found is that (insulin) sensitive individuals took the energy from carbohydrate in the meals and stored it away as glycogen in both liver and muscle," said Shulman.

In the insulin resistant subjects, the energy obtained from their carbohydrate rich meals was rerouted to liver triglyceride production, elevating triglycerides in the blood by as much as 60 percent and lowering HDL cholesterol (the good cholesterol) by 20 percent. "In contrast to the young, lean, insulin-sensitive subjects, who stored most of their ingested energy as liver and muscle glycogen, the young, lean, insulin-resistant subjects had a marked defect in muscle glycogen synthesis and diverted much more of their ingested carbohydrate into liver fat production, Shulman and his colleagues reported.

"What we see," he noted, "is alterations in patterns of energy storage. An additional key point is that the insulin resistance, in these young, lean, insulin resistant individuals, was independent of abdominal obesity and circulating plasma adi

Contact: Jennifer Michalowski
Howard Hughes Medical Institute

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