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Study Finds Molecular Link Between Obesity, Hypertension

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Most people know that obese individuals tend to have high blood pressure, but now British researchers have identified the molecular pathway that could explain that link.

In findings published in the Dec. 17 online issue of the New England Journal of Medicine, Sadaf Farooqi, of the University of Cambridge, and her colleagues demonstrated that signaling through the melanocortin-4 receptor (MC4R) helps to regulate blood pressure in humans.

Farooqi and her team studied blood pressure in 46 obese individuals who were missing one copy of the MC4R gene, and compared them to 30 obese individuals who had two normal copies of the gene. Individuals in the MC4R-deficient population tended to have slightly lower blood pressure values than did the control group (123/73 vs. 131/79), and less hypertension overall.

"The people where the MC4R gene is not working correctly actually were protected from high blood pressure," Farooqi explained.

As it turns out, these individuals appeared to have what Farooqi called "impaired sympathetic tone," which is that automatic part of the nervous system that controls the so-called "fight or flight" response to stress, and which apparently mediates this protective effect.

One aspect of the autonomic nervous system, for instance, involves the increase in heart rate that accompanies waking. In both study populations, the heart rate while sleeping was identical and increased upon waking. But the size of the increase in the two groups differed, with MC4R-deficient individuals' heart rate increasing less than control individuals.

Next, Farooqi teamed up with scientists at Eli Lilly, the pharmaceutical company, to test an MC4R agonist -- an experimental compound that works by inducing signaling through the MC4R receptor. The drug is in development as a potential anti-obesity medication, though this study was not assessing its effect on weight loss. Instead, the team looked at the drug's effect on blood pressure in 28 obese individuals (none of whom were MC4R-deficient).

What they observed was an acute, dose-dependent increase in blood pressure upon drug treatment, Farooqi said.

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