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The
science of fat
Photo by Chris Hammond
Dr. Sukhinder Kaur
By
Alexander Dalziel
SPARK Correspondent
Next time you prepare to bite into those deep-fried fast foods,
you might want to remember the findings of Dr. Sukhinder Kaur
of Memorial’s Department of Biochemistry.
For many years now Dr. Kaur has been delving deep into how fat
and DNA interact in human cholesterol metabolism. As of late
she has turned her attention to saturated and polyunsaturated
fats.
“My research is to study the regulation of genes involved
in cholesterol metabolism by various dietary fats and cholesterol,”
Dr. Kaur told the Gazette. “Why are saturated fats bad and
polyunsaturated fats good? And when we do consume these different
fatty acids, how do they regulate body metabolism, in particular
cholesterol metabolism?”
Cholesterol plays an important role in the human body, making
up the membranes of cells. There are two types of blood cholesterol,
the low-density lipoprotein (LDL) cholesterol and high-density
lipoprotein (HDL) cholesterol. Lipoproteins travel around the
body in blood plasma, the liquid surrounding blood cells.
These two types of lipoproteins are central to Dr. Kaur’s
research: “LDL is bad cholesterol, and HDL is good cholesterol,”
Dr. Kaur summarized. This distinction is based on the amount
of fat each contains. If a person consumes too much saturated
fat, the body creates too much LDL, which is a contributing factor
in the build up of the plaque that leads to clogged arteries
and even coronary heart disease.
The relationship between saturated fats and LDL was known, but
the molecular process behind it was not. Dr. Kaur and her lab
team did have some clues to go on. The process, according to
earlier research, was closely related to the gene that produces
the cholesterol ester transfer protein (CETP). “Increasing
CETP levels increases the amount of ‘bad’ cholesterol,”
Dr. Kaur said. “Previous studies have shown that saturated
fats and cholesterol increase CETP levels, but no one knows how
and why.”
After plenty of intensive lab work, she and her team have come
up with some initial answers.
The method for the production of cholesterol at the molecular
level deals with how DNA “transcribes,” or in other
words, how it informs cells about what they have to do. “There
are certain proteins called ‘transcription factors,’”
Dr. Kaur explained. “These are proteins that bind to specific
regions in the DNA. That’s how they control the amount of
protein being made – whether there will be more or less
[of a certain type] of protein being made.”
But transcription factors cannot do the work alone; they need
ligands in order to bind to the DNA. Ligands team with particular
transcription factors to determine where the binding will take
place. According to Dr. Kaur, this is where the fats come in:
“Our results show that fats act as ligands to bind transcription
factors and regulate the CETP gene, and this results in alterations
in the production of LDL or HDL.
“Different types of fat will have different types of impacts
on the regulation of CETP,” Dr. Kaur has concluded. “When
saturated fats are consumed, they eventually end up binding the
transcription factors to the gene that produces CETP, thus sending
more LDL, the ‘bad cholesterol’, into the bloodstream.
On the other hand, the consumption of polyunsaturated fats does
not result in the production of CETP, and thus it lessens the
amount of LDL.”
To achieve these results, Dr. Kaur used cultures of human tissues
and “transgenic” mice, which have human DNA spliced
into their genes.
According to Dr. Kaur, this work has direct applications in the
area of everyday dietary habits. “Many foods advertise themselves
as being low in saturated fats or as low in cholesterol,”
she pointed out. “For instance, we have looked at the regulation
of genes by fish oil and seal oil and how these interact with
other fats and cholesterol. Is it really beneficial to consume
them?”
Her work showed that yes, they are beneficial. “They are
good for you because they do not raise your blood cholesterol
level. If your blood cholesterol is normal, then your risk of
heart disease is low,” she said. She stressed, however,
that there still remains a good deal to be learned, and her research
will continue to study the exact mechanism behind this. “We
are interested to find out exactly how such foods lower blood
cholesterol levels.”
Dr. Kaur has picked up some other leads on the effects of cholesterol.
“Saturated fats are also directly linked to cancer,”
she stated. “My future research goal is to look into whether
different fatty acids regulate cell death, and how that is linked
to cancer.”
This will be another important step in understanding the molecular
foundations of human health.