The MCG research helps illustrate the need to pay particular attention to the cardiovascular side effects of potential new anti-obesity drugs as well, experts say. In an accompany editorial, Dr. Allyn L. Mark, Carver Professor of Medicine, Center on Functional Genomics of Hypertension at the University of Iowa Carver College of Medicine, noted the irony that despite lower body fat, mice with disturbed PTP1B had higher blood pressure than control animals. "Unfortunately several of the interventions that inhibit appetite, increase metabolism and decrease adiposity (fat) may increase (not decrease) sympathetic activity and arterial pressure," he writes. "This may complicate the safety of potential anti-obesity drugs," and emphasizes the importance of evaluating the cardiovascular impact of potential new therapies.

Now MCG scientists want to develop markers so one day people determine their PTP1B expression through a blood test. They also want to learn more about exactly how leptin increases blood pressure to see if there are ways to target some of the downstream impact of missing or mutated PTP1B.

"We want to look the impact on the kidneys and angiotensin 2," says Dr. Eric J. Belin de Chamtem-le, postdoctoral fellow in Dr. Stepp's lab and the study's first author. The kidneys, which determine how much sodium and water are excreted from the body, are major players in blood pressure regulation. Renin, which is secreted by the kidneys, constricts blood vessels to help blood pressure increase when blood volume gets low.

They want to know if leptin is acting directly on the kidneys or whether it's an indirect result from leptin's action in the brain. They suspect it's primarily a brain effect that they want to pursue by using mice with leptin deficits localized to the brain.

Source: Medical College of Georgia