Research team receives $10.6 million to study obesity and hypertension

Researchers at the University of Iowa and colleagues at Cornell University have received a five-year, $10.6 million grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, to continue their work investigating the biological links between high blood pressure and obesity.

According to the American Heart Association, one in three Americans, or about 100 million people, has high blood pressure, and nearly 75 million adults are obese. Hypertension and obesity increase the risk of cardiovascular diseases including stroke, heart attack, heart failure, and kidney failure, and obesity promotes diabetes, which also promotes cardiovascular disease. It is estimated that 300,000 deaths annually can be attributed to the cardiovascular complications of obesity.

Curt Sigmund

“Obesity and hypertension remain a serious health problem worldwide, in particular in Western societies where the incidence of hypertension and obesity-associated hypertension continues to rise,” says Curt Sigmund, UI professor and chair of pharmacology, and principal investigator for the grant.

The brain plays important roles in regulating both blood pressure and body weight, and abnormalities in various neural pathways can cause both hypertension and obesity. In particular, UI researchers have found growing evidence that hormones, which act in the brain, play a significant role in hypertension.

Earlier research by the UI team uncovered an unexpected association between how two hormones, angiotensin and leptin, act in the brain to control not only blood pressure but also processes that regulate food intake and energy expenditure.

“Although the past decade has seen a tremendous increase in our understanding of the neurobiology of blood pressure and body weight regulation, many of the fundamental central neural mechanisms, which go awry and lead to hypertension and obesity remain undefined,” says Sigmund, who also holds the Roy J. Carver Chair in Hypertension Research, and is a professor of pharmacology, internal medicine, and molecular physiology and biophysics in the UI Carver College of Medicine. “The new research funded by this grant will clarify these important mechanisms, and may lead to improved treatment for cardiovascular and metabolic dysfunction in hypertension and obesity-related hypertension.”

The long-term goals of the on-going project include identifying and clarifying the fundamental mechanisms by which angiotensin and leptin control blood pressure and body weight in both hypertension and hypertension associated with obesity. The researchers also will investigate the role that oxidative stress and abnormal protein folding in brain cells might play in regulating blood pressure and energy balance, and will study a family of genes involved in a rare genetic disease that may play a broader role in blood pressure control.

“The project is a great example of successful interdisciplinary research,” Sigmund adds. “Our team includes UI researchers from five departments (pharmacology, internal medicine, anatomy and cell biology, pediatrics, and psychology) from two colleges (the Carver College of Medicine and the College of Liberal Arts and Sciences), as well as a fruitful collaboration between the UI and Cornell University.”

The multidisciplinary nature of Sigmund’s team mirrors the approach of the UI Obesity Initiative, which aims to draw together researchers from across the campus to tackle obesity as a complex condition influenced by many different factors, including environment, genetics, physiology, behavior, community, and economics.

In addition to Sigmund, the new project’s leaders are Allyn Mark, M.D., UI professor of internal medicine; Kamal Rahmouni, Ph.D., UI associate professor of pharmacology and internal medicine; and Robin Davisson, Ph.D., professor at Weill Cornell Medical College and Cornell University. Martin Cassell, Ph.D., UI professor of anatomy and cell biology; and L. Phillip Sanford, Ph.D., director of the UI Transgenic and Genome Manipulation Facility, are the project’s core leaders; and Justin Grobe, Ph.D., UI assistant professor of pharmacology; Val Sheffield, M.D., Ph.D., UI professor of pediatrics and a Howard Hughes Medical Institute investigator; and A. Kim Johnson, Ph.D., UI professor of psychology, are collaborators. The grant is titled “Genetic and Signaling Mechanisms in the Central Regulation of Blood Pressure” (grant number: P01HL084207-06A1).