Insulin, a hormone long recognized as a generator of fat, also keeps fat in the liver under control, according to a new study in the July issue of Cell Metabolism. The newly discovered role for insulin may explain how an organ frequently flooded with the fat-building hormone normally stays trim and also suggests new dietary strategies and treatments to avoid fatty liver, a growing healthcare epidemic, said the researchers.

Insulin produced by the pancreas allows cells to take up glucose from the bloodstream and burn it for energy. In the liver, insulin promotes the synthesis and storage of lipids and carbohydrates and blocks their breakdown and release into the bloodstream. A failure to make or respond to insulin in people with diabetes causes blood sugar levels to rise.

The current study uncovered a new mechanism whereby acute insulin pulses limit fat synthesis in the liver. This protective mechanism fails in obese mice and mice with persistently high levels of insulin, the researchers also found.

The findings suggest that periods of fasting between meals play a critical role in maintaining a lean and healthy liver by allowing insulin levels to rise and fall, said study lead author Sonia Najjar of the Medical University of Ohio.

Furthermore, she said, the results emphasize the central role of the liver in metabolic control. A liver overwhelmed with insulin--as can occur in those who overeat--may become resistant to the hormone, leading to greater fat production and visceral weight gain. Resulting hikes in blood sugar and fat can also spell diabetes and heart disease, Najjar added.

"When we eat, the pancreas produces insulin, which stimulates the absorption of sugar and fat by the liver," Najjar said. "But in today's Western society, large portions and frequent munching may lead insulin levels to remain high all the time. In that case, the liver no longer perceives pulses of the hormone and becomes resistant."

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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
19-Jul-2005

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