Metabolic syndrome -- don't blame the belly fat

[Guest guest]

Metabolic syndrome -- don't blame the belly fat

Mon, 2007-07-16 14:58 — BJS

Abdominal fat, the spare tire that many of us carry, has long been

implicated as a primary suspect in causing the metabolic syndrome, a

cluster of conditions that includes the most dangerous heart attack

risk factors: prediabetes, diabetes, high blood pressure, and changes

in cholesterol.

But with the help of powerful new imaging technologies, a team of

Medical Institute (HHMI) researchers at Yale University

School of Medicine has found that insulin resistance in skeletal

muscle leads to alterations in energy storage that set the stage for

the metabolic syndrome.

Insulin resistance is a condition in which the body's cells become

resistant to insulin, a hormone secreted by the pancreas that plays an

essential role in regulating the carbohydrates, lipids, and proteins

obtained from food.

The new study, published July 16, 2007, in the Proceedings of the

National Academy of Sciences (PNAS), demonstrates that insulin

resistance in skeletal muscle -- caused by decreased ability of muscle

to make glycogen, the stored form of carbohydrate from food energy --

can promote an elevated pattern of lipids or fats in the bloodstream

that underpins the metabolic syndrome.

The study was led by HHMI investigator Gerald I. Shulman and Kitt Falk

sen, both of the Yale University School of Medicine. Coauthors of

the paper were from Yale and Harvard Medical School.

The metabolic syndrome is a very common metabolic abnormality and the

prevalence is growing. However, the underlying factors that cause it

are poorly 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.

To begin to shed light on the earliest molecular events that lead to

the metabolic syndrome, Shulman and his colleagues used powerful new

magnetic resonance imaging techniques to observe how nutrients are

channeled in the body in 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 adipocytokines, suggesting

that these abnormalities develop later in the development of the

metabolic syndrome. "

The new findings promise to help untangle the early molecular events

of a syndrome at the root of one of the world's most significant

health issues. " Knowing how insulin resistance alters energy storage

before it leads to more serious problems can help those susceptible

prevent the onset of the metabolic syndrome, " Shulman said.

Another key observation was that skeletal muscle insulin resistance

precedes the development of insulin resistance in liver cells, and

that fat production in the liver is increased. " 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 " Shulman said.

The good news, according to Shulman, is that insulin resistance in

skeletal muscle can be countered through a simple intervention: exercise.

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