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Having too little ‘beige fat’ can send blood pressure levels skyrocketing, increasing the risk of serious problems like heart attack and stroke, scientists say.
It has long been known that being overweight can trigger high blood pressure, also known as hypertension, and hypertension can cause heart disease.
However, until now, the relationship’s underlying biology had eluded scientists.
Researchers have shown how a type of fatty tissue that helps the body burn energy, also directly influences blood pressure control.
In the study, spearheaded by experts at The Rockefeller University, New York, the team studied mice that had been genetically altered so they couldn’t form this type of fat, dubbed beige fat – which closely resembled human brown fat.
Also known as brown adipose tissue, brown fat’s main role in the human body is to turn the food we eat into body heat, and it is also activated in cold temperatures, keeping us warm.
It is typically found in the neck and upper back as well as around the kidneys and spinal cord.
Humans lose most brown fat after they pass infancy, but it previous research found that it can be generated through exercise, sleeping well and frequently exposing yourself to the cold.
When looking at the mice, the Rockefeller researchers found that the loss of beige fat made blood vessels more sensitive to one of the body’s strongest pressure signals, driving up blood pressure.
Publishing their findings in the journal Science, the researchers said: ‘We now know that it’s not just fat per se but the type of fat – in this case beige fat – that influences how the vasculature functions and regulate the whole body’s blood pressure.’
For the study, the team engineered mouse models that were otherwise healthy, other than their complete lack of beige fat.
Mascha Koenen, a postdoctoral fellow in the Cohen lab and study co-author, said: ‘We wanted the only difference to be whether the fat cells in the mouse were white or beige.
‘In that way, the engineered mice represent a healthy individual who just happens to not have brown fat,’ he continued.
They found that the fat that wrapped around the blood vessels of these mice began expressing markers of white fat – crucially including angiotensinogen, a precursor to a major hormone that is known to increase blood pressure.
The mice all had hypertension and showed early signs of heart damage, including the build up to stiff connective tissue around the blood vessels.
This process, known as fibrosis, makes blood vessels less flexible, inhibiting normal expansion and contraction and restricting blood flow.
Single-cell sequencing also revealed that cells void of any beige fat triggered a gene program which promotes stiff, fibrous tissue, forcing the heart to pump harder and in turn raising blood pressure.
The team concluded that fat cells lacking beige fat were releasing certain signalling enzymes into their surroundings, which was enough to switch on genes responsible for fibrosis.
One of these enzymes- called QSOX1 – has already been implement in cancer research, playing a significant role in the reshaping of tissue.
In healthy conditions, beige fat normally suppresses the production of this enzyme.
But when fat cells lose their beige fat, QSOX1 is rapidly produced, trigger a chain reaction that culminates in high blood pressure.
The team also highlighted that in existing clinical cohorts, patients who have mutations in PDM16 – the gene whose loss activates QSOX1 in mice – tend to have higher blood pressure.
This, they say, indicates their findings in mice studies translate well to humans.
They hope their work will pave the way for future research into how differences in fat surrounding blood vessels influences where disease is most likely to develop.
Dr Paul Cohen, a physician-scientist focusing on obesity and metabolic disease and study lead, said: ‘The more we know about these molecular links, the more we can move towards conceiving of a world where we can recommend targeted therapies based on an individual’s medical and molecular characteristics.’
It comes as an estimated 14million UK adults now live with high blood pressure – a figure that’s steadily rising.
Lack of exercise, poor diet and excess alcohol have long been blamed for the rise in hypertension. But the risk that chronic stress poses – particularly among the young – has fallen under the radar.
Rates are rising among the young and nearly 170,000 16- to 24-year-olds are estimated to be living with undiagnosed hypertension.
Of the 16million UK adults estimated to have high blood pressure, up to half are not receiving effective treatment, the British Heart Foundation says. And as many as five million are believed to be undiagnosed.
