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Vanderbilt researchers are studying how a high-fat diet impacts the brain. (iStockphoto)

High-fat dietís impact on brain explored

BY: BILL SNYDER

9/25/2009 - Does fast food mess with your brain?

That's one of the questions Vanderbilt scientists Kevin Niswender, M.D., Ph.D., and Aurelio Galli, Ph.D., hope to answer with the help of a $5.2 million “transformative” research grant from the National Institutes of Health (NIH).

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Their hypothesis: consumption of high-fat, high-sugar foods can disrupt insulin signaling in the brain, and its regulation of neurotransmitters involved in mood and behavior. This may explain “food addiction,” and could lead to new ways to treat obesity and diabetes.

“It's really very strange to be using this sort of addiction language for a metabolic disorder like obesity, but the basic mechanisms seem to fit,” said Niswender, assistant professor of Medicine.

Niswender and Galli's grant is one of 42 “transformative R01” (T-R01) grants awarded nationwide for the first time this fall by the NIH — and one of two awarded to Vanderbilt scientists.

Aurelio Galli, Ph.D.

Aurelio Galli, Ph.D.

The R01 research project grant is a major way the NIH supports research that is supported “by good preliminary data,” explained Galli, associate professor of Molecular Physiology & Biophysics.

In comparison, the T-R01 program, part of the NIH “Roadmap” initiative designed to accelerate the pace of biomedical research, supports the “bold concept,” he said, which has the potential to “change the way we think about a particular medical problem.”

In 2007, Galli and colleagues at Vanderbilt and the University of Texas in San Antonio reported that insulin, the hormone that governs glucose metabolism in the body, also regulates the brain's supply of dopamine.

Kevin Niswender, M.D., Ph.D.

Kevin Niswender, M.D., Ph.D.

They were among the first to find a link between decreased insulin signaling, which occurs in insulin-deficient (or Type I) diabetes, and altered dopamine signaling, which contributes to addiction, schizophrenia and attention-deficit hyperactivity disorder (ADHD), and which can cause cognitive problems.

Previously Niswender and colleagues identified the signaling mechanisms by which hormones like insulin and leptin regulate feeding.

In work done at Vanderbilt, his group has uncovered mechanisms by which high-fat diets contribute to brain insulin resistance, where insulin is present, but does not work effectively.

Galli, a biophysicist who studies drug addiction, and Niswender, a specialist in metabolism and diabetes, combined forces to ask the question: could consumption of “fast foods” and soft drinks sweetened by fructose disrupt insulin signaling in the brain in a way that leads to food addiction and obesity?

Because insulin resistance impairs the normal dopamine “reward pathway,” you may have to eat “more of the same high-fat, high-carbohydrate types of foods to give you the same amount of reward you used to get,” Niswender said.

“How many exposures to that sort of a meal does it take to induce these mechanisms in the brain?” he asked. “Are those mechanisms reversible? Do they reverse with weight loss? Can we identify new molecular targets for drug development to treat obesity with drugs?”

Galli and Niswender will try to answer these questions in molecular and animal studies, using a broad range of techniques. Ultimately, they would like to apply their findings to humans.

“We are equipped to go from the single protein to the human brain,” Galli said.

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