An intermediary between unsaturated fatty acids and the genome has been identified
Scientists at Wageningen University (the Netherlands), working under the guidance of Dr. Linda Sanderson, have demonstrated the enormous importance of the role played by dietary fats in the regulation of gene expression. Using a combination of several nutrigenomic approaches, the researchers found that unsaturated fatty acids control a large number of genes, and this occurs mainly through activation of the PPARa receptor (Peroxisome Proliferator Activated Receptor alpha – activated by the peroxisome proliferator receptor-alpha).
The PPARa receptor is found in many tissues, including the liver, heart and intestines. In response to the effects of a number of drugs, it activates certain genes. A similar reaction of the receptor is also observed when exposed to fatty acids and compounds with a similar structure. It is known that activation of the PPARa receptor reduces the level of triglycerides in the blood, which theoretically can be used to treat patients with lipid metabolism disorders.
As part of their nutrigenomic study, the scientists introduced individual fatty acids in the form of synthetic triglycerides into the diet of rats. Using microchips that allow simultaneous monitoring of the expression levels of thousands of genes, they have revealed with a high degree of accuracy changes in the expression of animal genes occurring in response to the introduction of various fatty acids into the diet. It turned out that the most significant effect has dehydracetic acid, the use of which causes changes in the expression of about 600 genes. Dehydracetic acid is found in fish and fish oil and is associated with a number of beneficial effects, including lowering plasma triglyceride levels and suppressing thrombosis.
The most important achievement of the author was the demonstration that unsaturated fatty acids almost completely lose their effectiveness in the body of animals deprived of the PPARa receptor. The literature contains a lot of data, according to which there are many receptors that presumably bind to fatty acids and change the expression of genes at the same time. Most of these receptors belong to the family of so-called "nuclear hormone receptors", which include receptors for steroid hormones and fat-soluble vitamins. However, their importance to living organisms was unclear. Recent evidence suggests that the PPARa receptor plays a much more important role.
Many of the genes activated by unsaturated fatty acids are involved in the breakdown of these compounds for energy. It is most likely that this mechanism protects the liver from the accumulation of unsaturated fatty acids harmful to hepatocytes. Most likely, this mechanism provides a decrease in plasma triglycerides when consuming fish oil.
Until now, scientists who have studied the effects of fat consumption have introduced mixtures of fatty acids into the diet of mice or humans, which made it difficult to study the effect of individual compounds on the body. The authors believe that the application of the nutritional/pharmacological intervention approach using synthetic triglycerides will set new standards for nutrigenomic research.
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