Big bellies have been seen for a long time now as the main cause for the metabolic syndrome, a group of conditions leading to heart attack: prediabetes, diabetes, high blood pressure, and high cholesterol. By using new powerful imaging technologies, a team of Howard Hughes Medical Institute (HHMI) at Yale University School of Medicine has discovered that insulin resistance in skeletal muscle is in fact the starter of the metabolic syndrome.

Insulin resistance means that the body's cells turn immune to insulin, a hormone synthesized by the pancreas, which inserts inside the cells the carbohydrates, lipids, and proteins obtained from food and floating in the blood.

Insulin resistance in skeletal muscle, causing low ability of the muscle to produce glycogen ("animal starch", the form through which glucose absorbed from the blood is stored in the muscle cell and liver), can lead to high lipids (fats) levels in the blood, a starter of the metabolic syndrome.

Despite the widespread metabolic syndrome, the underlying factors are not clearly understood. "The syndrome afflicts more than 50 million Americans and roughly half of all Americans are predisposed to it, making it one of the nation's most serious human health issues.", said lead researcher Gerald I. Shulman.

His team used powerful magnetic resonance imaging techniques to see how nutrients are metabolized in the body in both insulin-resistant and insulin-sensitive individuals. All the subjects were young, lean, non-smoking, healthy individuals with a sedentary life and matched for physical activity.

The insulin resistance volunteers displayed none of the typical factors believed to be involved in metabolic syndrome, like obesity and type 2 diabetes. "Our hypothesis was that the metabolic syndrome is really a problem with how we store energy from food. The idea is that insulin resistance in muscle changes the pattern of energy storage." said Shulman.

After the subjects ate two carbohydrates-rich meals, the team used the magnetic resonance spectroscopy to assess the production of liver and muscle triglyceride (fat storage form), and of glycogen (glucose storage form) (the human body turns all carbohydrates in glucose). "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.

But in the case of the insulin resistant individuals, all carbohydrates were rerouted to liver triglyceride production, rising triglyceride blood levels by up to 60 % and decreasing HDL cholesterol ("good cholesterol") by 20 %. "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," wrote the researchers.

"The insulin resistance, in these young, lean, insulin resistant individuals, was independent of abdominal obesity and circulating plasma adipocytokines, suggesting that these abnormalities develop later in the development of the metabolic syndrome." said Shulman.

Another issue: skeletal muscle insulin resistance was found to precede the emergence of insulin resistance in liver cells, and fat production in the liver was boosted.

"These findings also have important implications for understanding the pathogenesis of nonalcoholic fatty liver disease, one of the most prevalent liver diseases in both adults and children. The good news is that insulin resistance in skeletal muscle can be countered through a simple intervention: exercise," said Shulman.