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Sampath Parthasarathy, PhD, & Martha Belury, PhD

Award Name Pilot Grant

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Diabetic Hypertriglyceridemia: Exploring New Options

ParthasarathyThe Ohio State University Center for Clinical and Translational Science has awarded Sampath Parthasarathy, PhD, MBA, FAHA, and Martha Belury, PhD, RD, with a one-year pilot grant for their research about potential treatment options for diabetic hypertriglyceridemia.

Finding a commonality between high glucose, high oxidative stress, and triglycerides has been a passion and goal of Parthasarathy’s for a “long, long time,” he said. “The CCTS has offered me an opportunity to think how best I can link these three.”

Currently, few options are available for decreasing triglycerides. Fibrates are commercially available drugs that reduce triglycerides but should be used with caution because of their toxicity. Fish oil has also been found to be beneficial, but must be taken in large quantities in order to be effective.

BeluryThe research team is paying special attention to the role of pyruvic acid.

“Pyruvic acid has been a molecule of interest for long time because it’s the one that goes into the mitochondria and produces energy,” Parthasarathy said.

However, pyruvic acid is unstable. Though glucose produces pyruvic acid through energy metabolism, it also produces bad peroxide compounds, which can in turn break down pyruvic acid and cause a production of acetic acid outside of the mitochondria where it is needed.

Parthasarathy describes it as “taking coal not to the power plant, but somewhere in the waste dump…so the waste accumulates.”

As a result, the acetic acid accumulates on the triglycerides. This is what led Parthasarathy to question whether triglycerides are benign molecules or if they are capable of causing disease.

To find out, Parthasarathy is creating a compound that looks and acts like pyruvic acid, but preserves the cell’s own pyruvic acid by sacrificing itself. He is using an aspirin-like molecule called simple alpha-keto acid which, when destroyed, will enable the body to make its own aspirin. His second goal is to improve the efficiency of the mitochondria.

The results of the study may benefit those who are afflicted with ailments other than diabetes.

“Any person now in the United States who’s diagnosed with Type 2 diabetes is automatically assumed to have some cardiovascular disease,” Belury said. “We hope that this compound can help not only people who are obese and might be predisposed to diabetes, but even those who have heart disease and may or may not be showing signs of diabetes.”

The team is conducting its research on C-57 black mice with a leptin deficiency, meaning the mice are unable to regulate food intake and will become “diabetic-like” within a month. The mice will allow the team to track metabolites in the blood and examine the liver after the mice have been put down.

Understanding how the liver changed its metabolism of cholesterol is important in helping the mice become less diabetic-like.

The mice, which have an increased amount of triglycerides, will be treated with the simple alpha-keto acid compound. The goals of the treatment are to see whether triglycerides are reduced, mitochondrial functions are improved, and if it is beneficial to diabetes.

According to Parthasarathy, meeting even one or two of these goals would be beneficial in understanding if triglycerides can be controlled and whether or not that helps diabetes.

The long-term goals of the team include sharing their findings with other scientists, writing a larger grant to further understand the compound, and seeking funds from the NIH.

By Nicole Frie, Thursday, July 29, 2010

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