Leptin as the Link Between Obesity and Hypertension

Hypertension, chronically raised blood pressure, is very damaging. It is an important mechanism by which low-level molecular damage and disarray in aging is converted into structural damage to important tissues in the brain, kidneys, and other organs. It is so influential in aging that lowering of raised blood pressure reduces mortality and disease risk even without addressing the underlying causes of the condition. Obesity is well known to cause raised blood pressure, and researchers here identify a novel mechanism for this effect involving leptin signaling. Since leptin signaling does change with age, it will be interesting to see whether or not this mechanism also operates to a significant degree in the aging and hypertension of non-obese individuals.

There's no question that as body weight increases, so too does blood pressure. Now, in a study of mice, researchers have revealed exactly which molecules are likely responsible for the link between obesity and blood pressure. Nearly a third of American adults have high blood pressure, and only about half of those people have their blood pressure under control through medications and lifestyle changes. Hypertension can be especially difficult to treat in obese patients.

The new work revolves around leptin, a molecule that controls appetite and metabolism in response to food. Obese people often become resistant to leptin, so rising levels of the molecule after a meal no longer boost metabolism or cause a feeling of fullness. In response to this resistance, leptin levels continue to rise with obesity. Leptin has also been shown to increase blood pressure and, surprisingly, obesity doesn't change that link - even when people are resistant to leptin's effects on metabolism and appetite, their blood pressure rises in response to the molecule. Until now, researchers weren't sure why.

Previous studies had revealed that there were high levels of leptin receptors in the carotid bodies - tiny clusters of cells along the carotid arteries on either side of the throat that respond to changing levels of oxygen and carbon dioxide in the blood. Researchers wondered whether this could be where leptin affects blood pressure, completely separate from its effects on appetite and metabolism in the brain.

Researchers first confirmed that giving high doses of leptin to lean mice triggered a rise in blood pressure of 10.5 to 12.2 mm Hg, while having no effect on heart rate or food intake. Then, they repeated the experiment in mice without functioning carotid bodies. This time, the animals' blood pressure didn't change in response to leptin. Next, the team studied obese mice that had no leptin receptors - despite their weight, they had normal blood pressure. But when the researchers injected the genes for leptin receptors directly into the carotid bodies of these mice, the animals' blood pressure readings rose by 9.4 to 12.5 mm Hg.

Link: https://www.hopkinsmedicine.org/news/newsroom/news-releases/researchers-discover-new-treatable-pathway-known-to-cause-hypertension-in-obese-people

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