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(June 14, 2001, Gazette)

The science of fat

Dr. Sukhinder KaurPhoto 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.

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