NIH funds faculty research on how obesity leads to heart disease

Aug 14, 2018

Vishu Puri in his lab.

A faculty researcher at the Ohio University Heritage College of Osteopathic Medicine is one of the leaders of a new project to explore a chemical pathway by which changes in fat metabolism brought on by human obesity can lead to cardiovascular disease. The study, “Identifying a novel regulatory pathway of vascular function in obesity,” has been awarded a four-year, $2.2 million R01 (research project) grant from the National Institutes of Health.

The project, which could lead to the development of new drugs to combat diseases of the circulatory system, will be a collaboration by principal investigators Noyan Gokce, M.D., a professor at the Boston University School of Medicine, and Vishwajeet Puri, Ph.D., a professor in the Heritage College’s Department of Biomedical Sciences and Diabetes Institute.

Project extends a research partnership

The two researchers previously worked together studying obesity while Puri was at Boston University School of Medicine. Puri brings to the collaboration his basic science expertise in fat-cell biology, while Gokce, as cardiologist and director of echocardiography at Boston Medical Center, contributes clinical knowledge of the cardiovascular system.

“The obesity epidemic has developed into a critical health care problem as 69 percent of the U.S. population is currently overweight or obese,” notes a news release from Boston University. “This research will seek to characterize the relationship between obesity, adipose tissue dysfunction, insulin resistance and how these processes cause vascular disease.”

Heritage College Executive Dean and Ohio University Chief Medical Affairs Officer Ken Johnson, D.O., welcomed news of the NIH grant, citing the impact the study could eventually have on patient health. “The Heritage College has made a long-term commitment to expand and strengthen our research component by supporting the work of our faculty, hiring exceptional new researchers and improving our laboratory infrastructure,” Johnson said. “We’re seeing that commitment bear fruit in the form of projects like Dr. Puri’s, which has the potential to produce significant translational breakthroughs in the treatment and prevention of diseases associated with obesity.”

Looking closer at an important protein

Puri explained that the new study, already in progress, builds on past research into FSP27, a fat-specific protein that in 2007 he discovered to be associated with fat. He found that FSP27 plays a role in regulating insulin sensitivity and the metabolism of fat in human adipocytes (fat cells), and that in people with obesity and metabolic disease, FSP27 levels go down.

According to Puri, more recent research has discovered, quite unexpectedly, that the protein has other regulatory functions outside fat cells as well. “Surprisingly, we have found that it is actually associated with both angiogenesis and vascular function,” he said. In other words, FSP27 affects the function of endothelial cells (which make up blood vessels), how the vessels form and how well they dilate – which is an important factor in high blood pressure, heart disease and stroke.

According to a description by the researchers of their project, the lowering of FSP27 levels brought on by obesity is associated with “profound abnormalities” in blood vessel formation and function; finding out the specifics of this connection is the aim of the NIH-funded study.

Mice with human genes aid in the research

Part of the research in this study will involve genetically engineered mice that have been modified to express genetic material from humans with obesity, so that in the mice bodies, obesity-related changes in FSP27’s effects will be like those in humans. Clarifying how FSP27 regulates growth and function of blood vessels, the project description suggests, “may represent an important piece of the pathogenic puzzle linking obesity and cardiovascular disease.”

Use of the genetically modified mouse models will allow the researchers to study the regulatory mechanisms of FSP27 in the context of “whole body physiology,” making it easier to work toward developing a drug that could be effective in preventing cardiovascular disease. “That’s why NIH was so excited about this research,” Puri explained.