Warming beige fat may lower blood pressure, mouse study suggests

Not all fats are created equal. Studies using mice suggest that some types of fat in the body raise blood pressure, while other types of fat suppress the rise in blood pressure.

Excess body fat in humans has long been linked to high blood pressure and many other cardiovascular problems. However, there are two types of fat in the body. One is “brown” fat, which helps you burn energy and keep your body warm, and the other is “white” fat, which stores excess calories.

Lead author Dr. Paul Cohen, a cardiologist and physician-scientist at New York’s Rockefeller University, said brown fat had long been thought to decline after childhood. But about 15 years ago, it was discovered that adults retain some brown fat, which is primarily activated by exposure to cold. Furthermore, Cohen subsequently showed that higher levels of brown fat were associated with lower prevalence of obesity and hypertension.

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“We wanted to better understand how brown fat does this,” Cohen told Live Science.

Now, in a new study published January 15 in the journal Science, Cohen and his team showed that removing the gene that makes “beige” fat, the equivalent of adult brown fat in mice, converts all the beige fat around blood vessels into white fat. This caused the mice to develop high blood pressure.

The research team determined that the effect was due to an enzyme released from fat cells. Normally suppressed by beige fat cells, studies have shown that enzyme levels spike when beige fat is converted to white fat. This caused the blood vessels to become overly tense and blood pressure to rise.

“This is an important study that demonstrates for the first time how beige fat directly affects cardiovascular health,” said Lawrence Kazak, an associate professor at McGill University who studies the energy expenditure of brown fat and was not involved in the study.

It’s well documented that obesity affects blood pressure and cardiometabolic health at a systems level, Kazak told Live Science. However, he said the study highlights the “niche role” of beige fat and the mechanisms behind its “local effects” on blood vessels.

How fats control blood pressure

Cohen’s team began their research by deleting the Prdm16 gene from fat cells in laboratory mice, turning the beige fat around blood vessels white. This gene is highly active in beige fat and is known to act as a master regulator that helps maintain its energy-burning function rather than turning it into white fat.

The changes were obvious just by looking at the tissue, said first study author Maska Koenen, a postdoctoral fellow in Cohen’s lab. The beige fatty tissue, which normally looks dull and speckled with small water droplets, becomes pale and resembles normal white fat.

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Researchers observed that animals lacking beige fat had increased blood pressure, blood vessels became stiffer, more fibrous tissue accumulated, and they had difficulty relaxing as blood flowed through them.

The researchers then treated the mice’s blood vessels with a hormone called angiotensin II, which is known to constrict arteries and increase blood pressure, much like pinching a hose restricts water flow. Blood vessels in mice lacking beige fat constricted more strongly in response to hormones than blood vessels in normal mice.

To identify the mechanism behind this, the research team looked at molecular signals released by fat cells near blood vessels and identified an enzyme called QSOX1. This enzyme hardens the connective tissue around blood vessels, making them less likely to loosen.

Normally, the protein encoded by the Prdm16 gene suppresses the production of this enzyme. But in the absence of beige fat, QSOX1 levels spike, leading to stiffening of blood vessels and high blood pressure, the researchers concluded.

Importantly, the researchers found that deleting both beige fat and QSOX1 from mice prevented this chain reaction and the mice did not develop hypertension, concluding that QSOX1 is essential for driving this mechanism.

Beige fat in mice and brown fat in humans are known to produce heat. These contain large numbers of mitochondria, which are the cell’s energy factories and give tissues their brown color. However, Koenen pointed out that this thermogenic function is not related to the QSOX1 mechanism they identified. Their study instead highlights the additional role of beige fat as “secretory” cells that release important proteins into the blood.

Even if the beige fat cells are small, “they can have a big impact on whole-body physiology,” Koenen told Live Science. And this research may suggest new treatments for high blood pressure.

“You can imagine that molecules that can inhibit QSOX1 could be of therapeutic benefit,” Kazak suggested.

Cohen also believes that targeting QSOX1 could help scientists develop precision treatments for high blood pressure in the future. To combat this, he noted, we first need to learn more about this mechanism. Nevertheless, this study represents a “step forward” in studying the effects of QSOX1 inhibitors in humans.