April 14, 2016

Study spots possible new approach to prevent obesity

An international research team that included scientists from Vanderbilt University Medical Center has found a novel way to counteract obesity in mice — by stimulating the growth of blood vessels in fat tissue.

An international research team that included scientists from Vanderbilt University Medical Center has found a novel way to counteract obesity in mice — by stimulating the growth of blood vessels in fat tissue.

Their findings, published this week in the journal Cell Metabolism, could represent a new approach for preventing diet-induced obesity and its complications, including type-2 diabetes.

The study, led by researchers in Finland, focused on vascular endothelial growth factor B, or VEGF-B. When VEGF-B binds to its receptor, VEGFR-1, it displaces another growth factor, VEGF, which then binds to VEGFR-2.

These events induce angiogenesis, growth of blood vessels, in fatty (adipose) tissue. The researchers found they also improved insulin sensitivity. Release of lipids, or fat molecules, by adipose tissue decreased, and glucose uptake by muscle tissue increased, thereby preventing development of insulin resistance, a characteristic of type 2 diabetes.

“Finding ways to improve insulin sensitivity in obese humans is critical because impaired insulin sensitivity drives the progression of type 2 diabetes,” said Vanderbilt co-author Ian Williams. “The finding that increasing levels of VEGF-B improves insulin sensitivity demonstrates it may be useful therapeutically in the prevention of type II diabetes.”

Williams, a graduate student in the laboratory of David Wasserman, Ph.D., conducted the experiments that showed increasing levels of VEGF-B improved insulin sensitivity in obese mice. Wasserman, the Annie Mary Lyle Professor in the Department of Molecular Physiology and Biophysics, directs the Mouse Metabolic Phenotyping Center.

Fat tissue is an important target for preventing obesity and its complications. Healthy white adipose tissue stores fat and prevents excessive fat accumulation in other organs including the liver and the heart. Excess fat, in turn, contributes to systemic inflammation and insulin resistance.

Previous studies have found that increasing VEGF-B levels can reduce inflammation and improve insulin sensitivity in obese mice. The current study, led by Kari Alitalo, M.D., Ph.D., at the University of Helsinki, Finland, found that these effects are enhanced when the growth factor’s receptor, VEGFR-1, is also blocked.

“Downregulation of VEGFR-1, together with increased VEGF-B levels … could be a promising therapeutic strategy for counteracting obesity,” the researchers concluded.

Vanderbilt’s part of the study was supported by National Institutes of Health grants DK059637 and DK054902.