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Scientists ID molecular 'switch' in liver that triggers harmful effects of saturated and trans fats

BOSTON--Dana-Farber Cancer Institute researchers have identified a molecular mechanism in the liver that explains, for the first time, how consuming foods rich in saturated fats and trans-fatty acids causes elevated blood levels of cholesterol and triglycerides and increases one's risk of heart disease and certain cancers.

In the Jan. 28 issue of Cell, scientists led by Bruce Spiegelman, PhD, report that the harmful effects of saturated and trans fats are set in motion by a biochemical switch, or co-activator, in liver cells called PGC-1beta.

Until now, scientists lacked a detailed explanation of how saturated and trans fats caused an increase in blood cholesterol and triglycerides, while diets high in unsaturated and polyunsaturated fats did not. Evidence pointed to the liver, which is responsible for the body's synthesis of triglycerides and cholesterol, but the molecular chain of events from eating fats to the buildup of cholesterol and triglycerides in the blood were unknown.

"What we have found is a missing link, a mechanism by which saturated fats and trans fats can do their dirty work," said Spiegelman, who carries out basic research on fat cells and metabolic pathways in diabetes and cancer at Dana-Farber. "It offers the opportunity to try to understand what makes these fatty acids so deleterious, and what we need to avoid."

Moreover, it is possible that in the future, drug therapy might be used to "turn down" the mechanism, decreasing cholesterol levels and heart disease risk, explained Spiegelman, who is also a professor of cell biology at Harvard Medical School.

Saturated fats are found in fatty cuts of meat, whole-milk dairy products, butter, and palm and coconut oils; they are associated with higher risk of coronary disease. The healthier polyunsaturated fats are those that remain liquid at room temperature, such as various types of vegetable oils.

Trans-unsaturated fatty acids, or trans fats, are artifici
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Contact: Bill Schaller or Richard Saltus
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
27-Jan-2005


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