US researchers 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.
Their findings shed light on the ongoing dilemma in scientific circles as to how saturated and trans fats cause an increase in blood cholesterol and triglycerides, while diets high in unsaturated and polyunsaturated fats do not.
"What we have found is a missing link, a mechanism by which saturated fats and trans fats can do their dirty work," said Bruce Spiegelman, involved in the research at the US Dana-Farber institute.
Their findings could open up opportunities for food scientists currently working on technologies to slice out harmful trans fats from their food formulations.
Trans fatty acids (TFAs) are formed when liquid vegetable oils go through a chemical process called hydrogenation. Hydrogenated vegetable fat is used by food processors because it is solid at room temperature and has a longer shelf life.
But mounting evidence suggests the TFAs raise LDL (bad) cholesterol levels, causing the arteries to become more rigid and clogged. An increase in LDL cholesterol levels can lead to heart disease.
Demand for trans fat free food products is pushing new product developments, particularly in the US where incoming rules mean that by 1 January 2006 all trans fats in food products will have to be labelled on the nutritional panel.
Europe has yet to introduce a similar rule, but consumer organisations are pressing for such transparency and food makers are feeling market pressure to slice TFAs from their products.
In 2003 Denmark became the first country in the world to introduce restrictions on the use of industrially produced trans fatty acids. Oils and fat are now forbidden on the Danish market if they contain trans fatty acids exceeding 2 per cent.
Reporting their findings in Cell, 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), or 'bad' 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, say the scientists.
Co-activators join with other regulatory proteins called transcription factors in controlling the expression of genes.
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 manufacture more cholesterol, which it does in the form of very low-density lipoproteins.
The investigators noted that in mice fed high-fat diets, the PCG-1beta mechanism actually decreased cholesterol in the liver while increasing it in the bloodstream.
Full findings are published in the 28 January issue of Cell.
Joining other ingredients firms reaching out to target trans fat free formulations, US firm Cargill and Germany's Bayer CropScience announced a link up this week to bring a new speciality oil to market. The oil will not require hydrogenation, stated the two firms, that have combined their technologies on seed development to create the product.
Last year US firms Dow AgroSciences, Bunge and DuPont all launched their various brands of zero or low trans fat oils, joining ADM's NovoLipid.