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Taka
Fri, Mar-07-08, 06:15
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.po-
ne.0001681

SOURCE: http://www.sciencedaily.com/releases/2008/02/0802291-
43151.htm#

Marshall P
Tue, Mar-25-08, 17:16
Taka wrote:
> Receptor Revealed That Turns On Genes After Consuming
> Unsaturated Fats
>
> http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourn-
> al.pone.0001681

It's a shame they didn't include saturated fats. The article
says, "No saturated fatty acids were included because
triglycerides composed of common dietary saturated fatty acids
are solid at room temperature and could not be administered
orally." We humans don't find that a problem!

It also says something I find confusing. "Roughly, nuclear
receptors can be divided into three main groups: the endocrine
receptors that bind steroid hormones, the adopted orphan
receptors that bind dietary lipids, and the orphan receptors,
for which no ligand exists or still has to be identified."
That seems to imply that the only difference between orphan
receptors and adopted orphan receptors is that the ligands of
the latter have been identified.

"Adopted orphan receptors mainly function as lipid sensors by
altering the rate of transcription of specific genes in
response to changes in lipid concentration. These lipids
include oxysterols, bile acids, and fat soluble vitamins. In
addition, many adopted orphan receptors have been shown to
bind fatty acids and alter transcription in response to
changes in fatty acid concentration and/or composition,
including" Peroxisome-Proliferator Activated Receptors alpha,
beta, gamma, and delta.

They conducted experiments on PPAR-alpha -/- mice. Are you
familiar with Peroxisomal beta-oxidation and peroxisome
proliferation, Taka? It's something I just happened to chance
upon for the first time last night. (Chapter 30 in /Metabolism
at a Glance/.)

I'm surprised nobody's experimented with triglycerides
composed entirely of similar fatty acids before.

--
Marshall Price of Miami Known to Yahoo as d021317c