UT Southwestern receives $8 million NIH grant to study influence of brain and liver on inflammation

An $8 million grant from the National Institutes of Health will enable UT Southwestern Medical Center to investigate how fat tissue "talks" to the brain and the liver to promote inflammation-related disorders such as diabetes, heart disease and obesity.

The five-year grant takes advantage of expertise across the UT Southwestern campus, including faculty in the Touchstone Center for Diabetes Research, the division of hypothalamic research, and the departments of molecular genetics, internal medicine, and pharmacology.

"We're excited about tackling the complexity of how adipose [fat] tissue, the brain and the liver talk to each other and how this cross talk affects metabolism and inflammation," said Dr. Philipp Scherer, director of the Touchstone Center and principal investigator of the new project. "Getting this grant validates that the UT Southwestern metabolism group is doing state-of-the-art science."

In 2007, the Task Force for Obesity Research at UT Southwestern (TORS) received a $22 million NIH grant to enhance the institution's groundbreaking obesity research.

Dr. Scherer said that while there is clearly synergy with the TORS grant, this new effort is unique because it is specifically focused on phenomena related to inflammation, considered an underlying cause of metabolic disorders in humans.

"We're especially interested in understanding how the brain and the liver influence inflammation and how inflammation influences metabolism within other organs. Those are just a few of the questions our team plans to tackle," Dr. Scherer said.

Large fat cells are a particular area of focus, Dr. Scherer said, because they typically lead to increased cell death and systemic insulin resistance. Under normal circumstances, fat cells continue to grow until the extracellular matrix they've built around themselves is so strong that it's no longer flexible. Once that happens, the cells become inflamed and may contribute to the development of diabetes and heart disease.

"Our research benefits from a multidisciplinary approach and a willingness to share diverse expertise in working toward a common goal," he said. "Models generated for one project are pivotal for the other projects, just as the physiological or molecular expertise of one project leader will be critical to the success of future projects."

The five laboratories involved in the project will work individually on two common areas: identifying the critical sites of action for lipid-related inflammation in the periphery of the body as well as the brain, and identifying the biochemical signals that take place in the body after exposure to high-fat, lipid-rich foods. Lipids encompass a broad group of naturally occurring molecules, including fats, fatty acids and cholesterol.

Dr. Scherer said the team hypothesizes that the vagus nerve, which stretches from the brain stem into the abdomen, acts as a key link between the liver and the molecules involved in metabolism, such as hormones and lipids. Activation of this nerve affects parts of the brain associated with feeding and control of basic functions like heart rate and blood pressure.

The researchers also speculate, based on prior findings, that sensory neurons found within this nerve might be equipped to serve as a link between adipose tissue and the liver.

The award also will enable the researchers to characterize which genes are active in these vagus sensory neurons, Dr. Scherer said.