( uced solid fats used in shortening and ...)Scientists ID molecular 'switch' in liver that triggers harmful effects of saturated and trans fats

uced solid fats used in shortening and margarine, baked goods, and the oils used to cook french fries and other fast food. Studies have shown that trans fats not only raise LDL levels in the bloodstream but lower high-density lipoproteins (HDL, or "good" cholesterol) and may have even stronger adverse effects than do saturated fats.

The researchers report that when activated by harmful fats, PGC-1beta alters liver metabolism through a cascade of biochemical signals. The result is an upsurge in the liver's production of very low-density lipoprotein (VLDL) cholesterol, the precursor of low-density lipoprotein (LDL) cholesterol (known as the "bad" form of cholesterol) and triglycerides ?another fatty substance ?that are secreted into the bloodstream.

PGC-1beta belongs to a specific family of co-activators, proteins that interact with other proteins to turn genes on and off and adjust their activity, like a dimmer switch that varies the brightness of a light. Co-activators join with other regulatory proteins called transcription factors in controlling the expression of genes. Spiegelman and Jiandie Lin, PhD, the paper's lead author and a researcher at Dana-Farber, have previously discovered the PGC-1 co-activator family and several of its biochemical activities.

The Dana-Farber researchers made the discovery in searching for the function of PGC-1beta co-activator that was isolated in 2002. Experiments including the measurement of gene activity by microarrays showed that saturated and trans fats caused greater activity of the gene that makes PGC-1beta co-activator than did unsaturated fats.

The research also showed that when the fats triggered PGC-1beta, the co-activator interacted physically and turned up the function of sterol responsive element binding proteins. These important parts of the mechanism activate many key genes of lipid biosynthesis involving the pathways of cholesterol and triglycerides; these genes directed the liver to m
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Source:Dana-Farber Cancer Institute

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