Baltimore, MD—The Pew Charitable Trust has awarded Carnegie’s Steve Farber and colleague John F. Rawls of Duke University a $200,000 grant to investigate how dietary nutrients, such as fats, alter the ability to sense glucose in the gut—a process that involves the microbial ecosystem in the gut. Results from this research could reveal how microbes and nutrients in the gut environment interact and could provide new strategies to combat disorders such as diabetes and obesity.

Rawls has investigated host-microbe interactions, and Farber studies lipid­ metabolism. Together they will use the zebrafish for this work. Zebrafish are entirely clear while embryos and are ideal for observing developmental and metabolic mechanisms.

Recently, the two researchers showed that a high-fat meal lowers the ability for certain cells in the intestine to sense glucose. Glucose sensing is important for proper metabolic function. It is necessary for the release of the hormone insulin from pancreatic beta cells to reduce blood glucose concentration. This glucose sensing process is dependent on a particular type of gut bacteria.

The researchers will conduct novel imaging and genetic studies in zebrafish to determine how a high-fat diet silences intestinal cells’ ability to sense glucose, and to identify additional intestinal microbes that are involved in the process.

 “The goal of my lab has been to better understand the cell and molecular biology of lipids within digestive organs using the unique attributes of young zebrafish,” remarked Farber. “We know that defects in lipid metabolism underlie obesity, diabetes, and atherosclerosis. John and I have shown in prior work that specific microbes can promote the metabolism of dietary fats by the absorptive cells of the intestine, but we still don’t understand how the microbes pull this off. We hope that broadening this research to look at interaction between nutrients, microbes and different types of intestinal cells may provide us important insights into intestinal biology with implications for a host of human diseases.”

Image Caption: Pictured from left to right, are Steve Farber's graduate student Jay Thierer, Steve Farber, Rawls' former graduate student Ivana Semova, and John F. Rawls. They are on a rafting trip during a 2014 meeting “Molecular Mechanisms of Intestinal Lipid Absorption and Metabolism” held at Snowmass, CO.

 

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Developmental Biology