An estimated 60 million people in the United States are considered obese. Scientists know the excess weight puts these patients at higher risk for conditions such as heart disease, type 2 diabetes and cancer, but they don't always understand why. Work by Andreas Stahl, Ph.D., is helping shed light on the connections -– and suggesting new ways to prevent and treat these killer diseases.

Dr. Stahl's research focuses on "fatty acid transport proteins" (FATPs), molecules that help move fat from the bloodstream into the cells. There are six members of the FATP family, localized to different parts of the body, including the heart, liver, skeletal muscles (muscles that connect to and move bones) and kidneys. Working with mice, which develop many diseases in similar ways to humans, Dr. Stahl's lab is studying what effect blocking each FATP has on obesity and the subsequent development of illness.

This work has led to exciting discoveries, especially for diabetes. Mice lacking the FATP found in skeletal muscle, for example, stay thin even when fed a diet of high-fat food and "are completely protected from the development of type 2 diabetes," Dr. Stahl said. While it is too early to say that shutting this particular molecule off in humans would have the same effect, it makes for a promising potential drug target.

The team also recently showed that when obese, diabetic mice received genetic treatment to block production of FATP-5, which is found in the liver, they lost weight and regained sensitivity to insulin, essentially reversing their diabetes. The therapy also removed excess fat from the liver, which indicates that blocking FATP-5 might protect humans against an increasingly common inflammatory condition called fatty liver disease.

Encouraged by these discoveries, Dr. Stahl's team has started to explore the link between obesity and cancer –- a connection that clearly exists for tumors of the prostate, breast and several other areas, but is not well-understood. "The cancer field is not set up to look at metabolic disorders, and the metabolic field has traditionally not been interested in cancer. We have a model that allows us to bridge the gap and examine both," he said.

The ultimate goal, Dr. Stahl said, is to translate the hopeful findings in mice into better preventive treatments for patients. His lab has already started down this path through partnerships with local biotechnology companies to study compounds that can block FATP production in humans.

Outside the lab, Dr. Stahl has begun presenting his research to PAMF physicians. Increased information-sharing benefits both sides, he said. For doctors, it helps them better understand the link between obesity and disease, which may influence how they manage overweight patients. In turn, physicians may suggest interesting ideas for future research, such as whether preventing calorie absorption leads to longer life. "It has been a great way to connect to the physician community and get more people excited about this work," he said.

Dr. Stahl has also set up a Web site for community members and other professionals interested in learning more about his research, available at www.pamf.org/research/stahl.

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