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Compound in meat prevents diabetes, study suggests

WEST LAFAYETTE, Ind. -- A common type of fat found in red meats and cheeses may prevent diabetes, according to a research team from Purdue University and The Pennsylvania State University.

This information could lead to new drugs to help fight diabetes, or to improved dietary strategies to manage diabetes, the researchers say.

The study found that conjugated linoleic acid, a fatty acid known to scientists as "CLA," can prevent the onset of diabetes in laboratory animals, at least in the short term. The researchers say CLA appears to work as well as a new class of diabetes-fighting drugs, the thiazolidinediones, or TZDs.

Martha Belury, Purdue assistant professor of foods and nutrition, says: "If you inherit a genetic predisposition to adult-onset diabetes and you're obese and inactive, then you may well develop this disease. Our study suggests that CLA may help normalize or reduce blood glucose levels and prevent diabetes."

Adult-onset diabetes is the most common form of the disease, and it also is known as Type II or noninsulin-dependent diabetes. It affects about 15 million Americans, half of whom do not know that they have the disease because the initial symptoms can be so mild. (These symptoms may include hard-to-heal infections, blurred vision, tingling in the hands or feet, or dry, itchy skin.) Type II diabetes is caused by the body's inability to use insulin well, which causes a buildup of sugar in the blood. If left untreated, Type II diabetes can result in kidney problems, amputation of limbs, blindness, coronary heart disease or strokes.

The research on CLA's ability to control Type II diabetes was published in the March 27 issue of Biochemical and Biophysical Research Communications and will be presented at the American Diabetes Association annual meeting in Chicago on June 14. The research was funded by the National Cattleman's Beef Association, the Purdue Office of Research Programs, and Penn State.

In addition to Belury, members of the research team were Jack Vanden Heuvel, assistant professor of toxicology at Penn State; Louise Peck, assistant professor of foods and nutrition at Purdue; Silvia Moya-Camarena and Carla Portocarrero, graduate students at Purdue; Kwangok Nickel, postdoctoral researcher at Purdue; and Karen Houseknecht, assistant professor of animal sciences at Purdue and an adjunct assistant professor of endocrinology and metabolism at the Indiana University School of Medicine. A provisional patent on using CLA to treat diabetes has been issued to Purdue and Penn State.

According to Belury, CLA is a polyunsaturated fat found in meats and cheeses, and in lesser amounts in milk, yogurt, poultry, eggs and cooking oil. "It looks just like corn oil, but maybe just a little clearer," she says.

"It is in foods that are normally associated with saturated fats, but those foods can contain things that are good for you, too. The lesson here is that we still know so little about what is in foods naturally. We know that they contain certain vitamins and minerals, but there could be thousands of nutrients that we haven't even found yet."

Houseknecht says it is possible that CLA may have some advantages over current drug therapies on overall health. "When rats are given TZD, they get fatter. CLA makes them leaner, which has obvious advantages," she says. "In obese animals we saw a 10 percent reduction in body fat, and in lean animals we saw a 25 percent reduction in body fat."

CLA is available as a dietary supplement at health stores, but people shouldn't rush to consume large quantities of the compound until more is known about it, Houseknecht warns. "CLA could have some bad side effects, too," she says. "There never is a perfect drug, and so far there are no toxicology data for CLA."

The CLA research was conducted in a special breed of rat, called the Zucker Diabetic Fatty rat, which is obese and glucose intolerant and therefore mimics human adult-onset diabetes. The rats were given supplemental doses of CLA for two weeks. At the end of the experiment, all of the control rats had developed diabetes and none of the rats on CLA had developed the disease.

Previous studies with CLA have shown that it can prevent the onset of certain types of cancer and can reduce the number of mammary, skin and stomach tumors in laboratory animals.

According to Vanden Heuvel, CLA inhibits cancer in part by activating hormone receptors called PPARs, scientific shorthand for peroxisome proliferator-activated receptors. The research on CLA in cancer studies had shown that it affected a particular receptor called PPAR-alpha . The new drug to fight diabetes, TZD, works by activating a PPAR-gamma receptor, one that has the same chemical composition as PPAR-alpha but is structured slightly differently and may have a different biological function.

The researchers hypothesized that CLA might also have an effect on PPAR-gamma , and they found that it did.

Maureen Charron, diabetes researcher and associate professor of biochemistry at the Albert Einstein College of Medicine at Yeshiva University in New York, says she was excited when she heard of the findings. "The design of the study was novel and the results were remarkable," she says. "The findings in diabetic rats open the door to novel dietary intervention in Diabetes mellitus."

Charron suggests that more information is needed, however. "Caution must be taken in these therapies, because liver abnormalities have been recently reported in a small percent of troglitazone-treated patients. Similar side effects should be examined in CLA-treated rats." Troglitazone is one of the thiazolidinedione drugs.

According to the scientists, the CLA research is heading in several different directions. Belury, Peck and Vanden Heuvel plan to begin human trials on CLA and its effects on diabetes as soon as possible.

Meanwhile, Houseknecht plans additional animal studies to determine how CLA regulates glucose metabolism. "Our next step will be to see if the weight loss is real and sustained over time, and the second thing will be investigating whether CLA just delays the onset of diabetes for a time or if it actually prevents it from ever occurring. We also want to really nail down the effects on the whole body," Houseknecht says. "We really have a lot to learn about this compound. For one thing, we have not optimized the dose. We picked a dose that is effective in fighting cancer, and started there."

In addition to these projects, scientists in other disciplines already are working to take advantage of CLA's potentially beneficial effects. Researchers in the Purdue Department of Animal Sciences are looking at feeding CLA to hogs to see if that increases the levels of CLA in pork.

"If we can do this, and if higher doses of CLA are safe, we'll have a value-added pork chop that could help fight cancer and diabetes," Houseknecht says.

Sources: Martha Belury, (765) 494-0302; e-mail,;
Karen Houseknecht, (765) 494-4842; e-mail,;
Jack Vanden Heuvel, (814) 863-8532; e-mail,
Maureen Charron, (718) 430-2852; e-mail,;
Louise Peck, (765) 494-8236; e-mail,
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Writer: Steve Tally, (765) 494-9809; e-mail,;

NOTE TO JOURNALISTS: A copy of the journal article is available from Purdue News Service, (765) 494-2096. The citation is Biochemical and Biophysical Research Communications, Vol. 244, pp. 678 682. The data for this research will be presented in a poster at the American Diabetes Association annual meeting, June 13-16 in Chicago's McCormick Place Convention Center. The posters will be displayed in Exhibit Hall E; Karen Houseknecht will be available for questions in the general poster session on Sunday, June 14.


Dietary Conjugated Linoleic Acid Normalizes Impaired Glucose Tolerance in the Zucker Diabetic Fatty fa/faRat
Karen L. Houseknecht, Purdue University; John P. Vanden Heuvel, Pennsylvania State University; Silvia Y. Moya-Camarena, Carla P. Portocarrero, Louise W. Peck, Kwangok P. Nickel, and Martha Belury, Purdue University.

Conjugated linoleic acid (CLA) is a naturally occurring fatty acid which has anti-carcinogenic and anti-antherogenic properties. CLA activates PPAR-alpha in liver, and shares functional similarities to ligands of PPAR-gamma, the thiazolidinediones, which are potent insulin sensitizers. We provide the first evidence that CLA is able to normalize impaired glucose tolerance and improve hyperinsulinemia in the pre-diabetic ZDF rat. Additionally, dietary CLA increased steady state levels of aP2 mRNA in adipose tissue of fatty ZDF rats compared to controls, consistent with activation of PPAR-gamma. The insulin sensitizing effects of CLA are due, at least in part, to activation of PPAR-gamma since increasing levels of CLA induced a dose-dependent transactivation of PPAR-gamma in CV-1 cells cotransfected with PPAR-gamma and PPRE X 3-luciferase reporter construct. CLA effects on glucose tolerance and glucose homeostasis indicate that dietary CLA may prove to be an important therapy for the prevention and treatment of NIDDM.

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