Receptor Revealed That Turns On Genes After Consuming Unsaturated Fats

ScienceDaily (Mar. 4, 2008) -- Scientists from Wageningen University in
the Netherlands demonstrate the tremendous importance of dietary fat
as a regulator of gene expression. Via a combination of several
nutrigenomic tools Linda Sanderson and her colleagues reveal that
dietary unsaturated fatty acids govern a huge number of genes and do
so almost entirely via a special receptor called PPARa.

PPARa, which stands for Peroxisome Proliferator Activated Receptor
alpha, is a receptor that can be found in numerous tissues, including
liver, heart and intestine. It reacts to certain drugs by turning on
specific genes, yet can also respond to fatty acids and fatty acid
look-a-likes. Activation of PPARa is known to lower levels of
triglycerides in blood, providing a rationale for their use in
patients suffering from altered blood lipid levels.

In their nutrigenomics study, the research team led by Linda Sanderson
fed mice individual fatty acids in the form of synthetic
triglycerides. Using a technique called microarray, which allows for
monitoring the expression of thousands of genes simultaneously, they
were able to determine exactly which genes are turned on in the mouse
liver and which ones are turned off. The researchers found that the
fatty acid DHA has the most significant impact and changes the
expression of around 600 genes. DHA is found in fatty fish and fish
oil and has been associated with numerous health benefits, including
lowering of plasma triglycerides and decreasing blood clotting.

The most remarkable about the study is that the effects of unsaturated
fatty acids are almost entirely lost in mice that lack the PPARa
receptor.From the literature it is known that numerous receptors can
supposedly bind fatty acids and turn on genes. Most of these receptors
belong to the family of the so called 'nuclear hormone receptors',
which includes receptors that bind steroid hormones and fat soluble
vitamins. However, it was unknown how important they are in an actual
living animal. The new data show that PPARa is by far the most
important.

Many of the genes that are turned on by unsaturated fatty acids are
involved in breaking down fatty acids to generate energy. This
mechanism likely protects the liver cell from build-up of unsaturated
fatty acids, which is harmful to the cell. It also likely accounts for
the lowering of plasma triglycerides by fish oil.

Until now, all nutritional interventions with dietary fat in either
mice or human subjects involved a mixture of fatty acids. For that
reason, it has been very difficult to draw clear conclusions about the
effects of individual fatty acids. The mixed nutritional/
pharmacological intervention with synthetic triglycerides pursued by
Sanderson and colleagues represents a creative and novel way to study
the molecular effects of dietary fat. They expect that their approach
will set a new standard for many future nutrigenomic studies.

This research was recently published in PloS One.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001681

SOURCE: http://www.sciencedaily.com/releases/2008/02/080229143151.htm#