Research network yields significant findings related to obesity

In 2017, Vanderbilt University Medical Center was selected to be one of four U.S. medical centers in a Strategically Focused Research Network (SFRN) on Obesity funded by a four-year, $15 million award from the American Heart Association to study obesity and train future obesity-focused investigators.

Now, the findings of the research network have been published in a special report of the which hails the group’s work as “the beginning of innovative science, and, importantly, the birth of new collaborations and research partnerships to propel the field forward.”

The Centers for Disease Control and Prevention reports that during 2017 to 2018, the prevalence of obesity in the United States was 42.4%, increased from 30.5% during 1999 to 2002. In the United States, about one in five children and adolescents has obesity. Current estimates indicate that by 2030, the global prevalence of overweight and obesity may exceed 57%.

Researchers from VUMC and Vanderbilt University teamed with investigators from Johns Hopkins University School of Medicine, New York University Grossman School of Medicine and the University of Alabama at Birmingham to form the SFRN on Obesity. The group studied aspects of the increasingly common health problem that contributes to development of disorders that further reduce quality of life and life span, such as Type 2 diabetes and heart disease.

“The importance of sharply focused scientific collaborations such as the SFRN on Obesity cannot be overstated, particularly as the prevalence of overweight and obesity continues to escalate throughout the world,” said Kevin Niswender, MD, PhD, associate professor of Medicine at VUMC and director of the Vanderbilt center. “As a result of this American Heart Association-supported network, we have collectively taken several significant steps forward as we seek to more fully understand the causes of obesity, discover new therapeutic interventions and identify biomarkers to more precisely track both obesity and the success of weight loss.”

The four centers in the SFRN on Obesity were also tasked with developing a training program for investigators who would pursue obesity-related investigations. Despite obstacles created by the COVID-19 pandemic, AHA fellows were recruited at every center who presented their research at national and international conferences.

“This center accomplished many of the important goals of both VUMC and the AHA,” said Joshua Beckman, MD, professor of Medicine, who served as a training co-director for the center. “New knowledge was created that will advance our understanding of the interface between obesity and cardiovascular disease. New teams of investigators were brought together to attack these issues from basic, translational and clinical perspectives. New investigators were provided training in multiple disciplines to position them well to advance their careers and the science they will discover. All in all, it was a very VUMC-like effort — coming together to do big things.”

A goal of the VUMC center research was to further advance precision medicine approaches to treating obesity while reducing cardiovascular disease risk. Investigators focused on a particular drug target for diabetes and obesity, the glucagon-like peptide-1 receptor (GLP-1R), which has been shown to protect the heart and its arteries rather than increase the risk for cardiovascular disease.

As a result of the research of the VUMC team, it was determined that:

• Changes in the way the GLP-1R signals or communicates with cells, caused either by genetic variation or drug-like molecules, improve how cells respond to metabolic stress.
• GLP-1R activation does not directly alter how blood vessels function, but does improve other markers of cardiovascular disease risk.
• Using electronic health record data, curated for cardiometabolic outcomes, together with linked genotyping, offers novel approaches to understanding obesity and cardiometabolic risk heterogeneity.

Those involved in the SFRN on Obesity at VUMC include Niswender; training directors Alyssa Hasty, PhD, and Beckman; James Luther, MD, MSCI; former chair of the VUMC Department of Medicine Nancy Brown, MD; Nancy Cox, PhD; Quinn Wells, MD, PharmD, MSCI;  and postdoctoral fellows Megan Shuey-Henthorn, MSc, PhD; Rebecca Levinson, PhD; Megan Vogel, PhD; Mona Mashayekhi, MD, PhD; and Monica Bhanot, MD, PhD. Four Vanderbilt University undergraduate students also participated in the project.