WINSTON-SALEM, N.C. -- Researchers at the Wake Forest University School of Medicine are pursuing additional studies on why polyunsaturated fat in vegetable oil leads to less hardening of the arteries than the monounsaturated fat in olive oil.
Lawrence Rudel, Ph.D., professor of pathology (comparative medicine) and biochemistry, said that results from the first five years of a multidisciplinary program project grant were unexpected. Both monounsaturated fat and polyunsaturated fat lower the low density lipoprotein (LDL), the bad cholesterol, and it had been thought that the lower the LDL level, the better.
But it turns out that there are a number of varieties of LDL, he said. In monkey studies, the researchers found the vegetable oil group had a different LDL particle that was less likely to cause hardening of the arteries."
"The effect of monounsaturated fat in promoting a bad LDL composition was more important than previously anticipated," Rudel said. So the rapid rise in the use of olive oil in the past few years may be bad, not good.
As a result, the program project grant from the National Heart Lung and Blood Institute has just been renewed for five years, for a total of $7.4 million. The grant supports the primary research efforts of six faculty investigators and a number of research associates and technicians.
"Because this observation was unexpected and is contrary to the widely advertised health benefits of monounsaturated fat, the new grant period will be used to confirm the observation and investigate the means through which such an outcome could occur," Rudel said.
His project is one of five in the overall grant. The others are designed to learn about the factors that determine how diet may alter the lipoproteins that anyone may have in their blood. They include:
A project to explore whether defects in genes responsible for intestinal bile acid absorption can lead to high triglyceride levels by influencing production of very low density lipoproteins (VLDLs). The body's primary detergent, bile acid, which is made in the liver, is linked to the production of VLDLs containing apolioprotein B. The VLDLs transport high energy fatty acids as triglycerides throughout the body. Paul Dawson, Ph.D., associate professor of internal medicine (gastroenterology) and pathology, heads the project. High levels of triglycerides also are a risk factor for coronary artery disease.
A study to define factors in the diet that regulate formation of LDL. VLDLs are the precursors of LDL. Though the primary function of apolipoprotein B is to move triglycerides throughout the body, the product of VLDL triglyceride metabolism is LDL, which also conveys cholesterol to the walls of arteries. Gregory S. Shelness, Ph.D., associate professor of pathology (comparative medicine) heads this investigation.
An investigation to answer whether dietary fat type reduces high density lipoprotein (HDL), the good cholesterol, through increased destruction or decreased production of the various HDL particles. One surprising development was that people -- and nonhuman primates -- who consume polyunsaturated fatty acids end up with significantly lower concentrations of HDL, than do those eating diets with monounsaturated fats or saturated fats. That's surprising because polyunsaturated fat protects against coronary artery disease and doctors generally say the higher the HDL, the better. A research team headed by John S. Parks, Ph.D., professor of pathology (comparative medicine), already has found several varieties of HDL, some containing 2, 3 or 4 copies of apolipoprotein A-I, the major protein in HDL. It may be that the lower HDL in individuals eating polyunsaturated fat just means that HDL is working harder to remove cholesterol.
A team headed by Mary Sorci-Thomas, Ph.D., associate professor of pathology (comparative medicine), will make variants of apolipoprotein A-I (apo A-I) and study these variants to learn more about how HDL particles transport cholesterol. HDL needs apo A-I to act as the primary scavenger of cholesterol, taking it from the walls of the arteries and returning it to the liver for disposal. Both Parks's and Sorci-Thomas's projects will help define how HDL functions to protect against coronary artery disease.
Rudel said the team's researchers already had identified an enzyme in the liver called ACAT2 that may be responsible for developing the more harmful form of LDL, and they have cloned this enzyme. ACAT2 appears to be activated by monounsaturated fat, but not by polyunsaturated fat, and may promote the atherosclerosis-causing composition of LDL.
One goal of the new grant will be to determine whether this enzyme can be controlled by either diet or drugs and thus be an effective way to prevent coronary artery atherosclerosis.
"Our research to date has shown that, contrary to what has been widely assumed, dietary monounsaturated fat may not be protective against the development of coronary heart disease," Rudel said.
So it is important to determine as quickly as possible how olive oil and other monounsaturated fat function in the development of coronary artery disease, he said.
Rudel said that in addition to high LDL concentrations, some LDL particles may have modified compositions that cause more atherosclerosis than other LDLs, and the type of fat in the diet is a major factor in determining LDL composition.
Saturated fat, most often from animal products, promotes both a more atherogenic composition of LDL and a higher concentration of LDL cholesterol in the blood, he said. By contrast, while monounsaturated fat also promotes a bad composition of LDL, it also appears to lower the level of LDL cholesterol in the blood. So there is both a good and bad effect.
"The observation that monounsaturated fat produced both good and bad results for LDL prompted a study in nonhuman primates of the direct effect of monounsaturated fat on coronary artery atherosclerosis, the cause of heart attacks."
In the monkeys, monounsaturated fat lowered LDL and simultaneously raised HDL (high density lipoprotein, the good cholesterol) -- the same as it does in people, "but the extent of coronary artery atherosclerosis was the same as the monkeys who were fed saturated fat," he said.
In other words, despite the seemingly positive effect on the ratio of LDL to HDL that cardiologists ordinarily consider to be important, the monkeys still got hardening of the arteries.
"The comparison group of monkeys fed polyunsaturated fat -- vegetable oil -- has less coronary artery atherosclerosis even though the degree of the lowering of LDL cholesterol was the same as in the monkeys fed the olive oil."
Contact: Robert Conn, Jim Steele or Mark Wright at 336-716-4587