But the combination of missing or mutated PTP1B and too much leptin means increases in constriction are too strong to turn off.
Mice missing PTP1B tend to have lower body fat but high blood pressure, not usually what you see in people, Dr. Stepp notes. While this single gene can't explain every combination of body size and blood pressure found in nature, it could help explain why some skinny people are hypertensive and why others who get fat are as well.
"It's a vulnerability gene," he says. "If you stimulate leptin in individuals who can't activate their protective mechanisms, they are going to get hypertension. This tells us there are a lot of people and diseases
And what about those people who have great blood pressure? They likely have well-functioning PTP1B, he notes. Interestingly, PTP1B often is over expressed in obese people, which is good for the blood pressure but bad for leptin's positive effect on metabolism.
"I think we have identified at least a couple of new pieces of information that clarify the relationship between obesity and hypertension," Dr. Stepp says. "We have identified a gene that, if it's not functional, will greatly increase the extent to which a metabolic signal from leptin translates into a cardiovascular signal. We also have identified a protective mechanism that, if it's not working, contributes to hypertension."
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 Hyper
|Contact: Toni Baker|
Medical College of Georgia