Newswise — Vanderbilt University Medical Center (VUMC) is one of four centers receiving a $15 million, four-year research award from the American Heart Association (AHA) to provide cutting-edge research on obesity as part of its sixth Strategically Focused Research Network (SFRN). Researchers will team with Johns Hopkins University, New York University Medical Center and the University of Alabama at Birmingham to study different aspects of the common health problem that increases risk for heart disease, stroke and other serious issues. Nearly 70 percent of U.S. adults are overweight or obese, with total health care costs attributable to obesity estimated to reach $957 billion by 2030. “This is a unique and prestigious mechanism that the AHA has developed to fund cutting-edge research,” said Kevin Niswender, M.D., Ph.D., associate professor of Medicine at VUMC, staff physician for the Tennessee Valley Healthcare System and principal investigator for the Vanderbilt center. “The AHA selects four proposals in the country and forms a research network around a particular topic.” Vanderbilt has previously been awarded a SFRN center aimed at preventing heart disease and stroke that is led by David Harrison, M.D., director of the Division of Clinical Pharmacology. Each center in the SFRN has four components — a basic science project, human translational research project, population-based project and postdoctoral fellowship training that is funded within the center. Another emphasis is to develop new collaborations both within the network and within the VUMC center, Niswender said. Vanderbilt’s research is focused on recent findings that a particular drug target for diabetes and obesity, the glucagon-like peptide-1 receptor (GLP1R), has been shown to be cardio-protective rather than increase the risk for cardiovascular disease. “Most of our diabetes drugs that control blood glucose cause weight gain and actually perhaps increase risk for cardiovascular disease down the road,” Niswender said. “This is a real game changer.” A goal of the VUMC center is to develop precision medicine approaches to treating obesity while reducing cardiovascular disease risk. “We will use cutting edge tools to understand how genetic variations that some people have in the GLP1R, and how a certain drug that activates the receptor, are cardio-protective — is it weight, is it a vascular effect or is it something else?” Niswender said. The drug, Liraglutide, a GLP1R agonist that is FDA approved for the treatment of obesity, is also cardio-protective. Department of Medicine Chair Nancy Brown, M.D., who is an expert in cardiovascular and vascular function, is leading a project within the SFRN, in collaboration with Professor of Medicine Joshua Beckman, M.D., to compare the GLP1R-dependent cardiovascular effects of Liraglutide with dietary weight loss without medication. The group will determine whether genetic variation in the GLP1 receptor affects responses to Liraglutide. Heidi Silver, Ph.D., research associate professor of Medicine, will oversee weight loss treatment. “The ability to collaborate across basic, patient-oriented and genetic epidemiological studies to address a major health problem is one of our strengths here. I feel very excited to be part of this research and this group,” said Brown, also the Hugh Jackson Morgan Professor of Medicine and Pharmacology. Another project within the SFRN led by Vanderbilt Genetics Institute Director Nancy Cox, Ph.D., professor of Medicine, and Quinn Wells, M.D., assistant professor of Medicine, will make use of unique Vanderbilt resources, including BioVU, the largest university biobank in the world linked to a long-standing and high quality electronic health record. “We will use bioinformatics with the rich data we have to identify different subtypes of obesity and learn how those subtypes affect risk of cardiovascular disease and other health consequences of obesity, as well as whether the subtypes may respond differently to different medications,” said Cox, Mary Phillips Edmunds Gray Professor of Stem Biology and Tissue Regeneration. “This has been a really gratifying team effort, and Quinn and I are very excited to have the opportunity to work on this science with this team.” Alyssa Hasty, Ph.D., associate dean for Faculty Development of the Basic Sciences and an expert in the inflammation in adipose tissue, will oversee the training program. In addition to Vanderbilt, Johns Hopkins University researchers are investigating the role of time-restricted feeding on obesity; New York University Medical Center researchers are studying a receptor believed to slow metabolism to see if it’s blocking effective weight loss after lifestyle interventions or bariatric surgery; and University of Alabama at Birmingham researchers are looking at how mothers with obesity, metabolic syndrome and gestational diabetes may influence their children’s weight and health long after birth.
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