Scientists have discovered a crucial link between the presence of 'beige fat' and the regulation of blood pressure, a finding that could revolutionize understanding and treatment of hypertension, a leading cause of heart attack and stroke. While the connection between being overweight and high blood pressure (hypertension) has long been established, the specific biological mechanisms underlying this relationship have remained elusive until now. New research highlights how a particular type of fatty tissue, known as beige fat, which aids the body in burning energy, directly impacts the control of blood pressure.

Spearheaded by experts at The Rockefeller University in New York, the study involved genetically modifying mice to prevent the formation of beige fat, a tissue that closely resembles human brown fat. Brown adipose tissue, or brown fat, plays a vital role in converting food into body heat and is activated by cold temperatures, helping to keep us warm. In humans, it is typically located in the neck, upper back, and around the kidneys and spinal cord. While most brown fat is lost after infancy, previous research indicates it can be generated through physical exercise, adequate sleep, and regular exposure to cold.

The Rockefeller researchers observed that in mice lacking beige fat, blood vessels became notably more sensitive to the body's powerful pressure signals, consequently driving up blood pressure. Publishing their findings in the esteemed journal *Science*, the team emphasized: "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 scientists engineered mouse models that were otherwise healthy, with the sole distinction being the complete absence of beige fat. Mascha Koenen, a postdoctoral fellow and co-author, explained their approach: "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."

They discovered that the fat surrounding the blood vessels in these mice began to express markers characteristic of white fat. Crucially, this included angiotensinogen, a precursor to a major hormone well-known for its role in increasing blood pressure. All the mice in the study developed hypertension and exhibited early signs of heart damage, including the accumulation of stiff connective tissue around the blood vessels. This process, termed fibrosis, reduces the flexibility of blood vessels, hindering their normal expansion and contraction and thereby restricting blood flow. Hypertension occurs when the pressure of blood pushing against the heart walls is consistently too high, which damages arteries and restricts blood flow.

Further investigation using single-cell sequencing revealed that cells devoid of beige fat initiated a specific gene program that promotes the development of stiff, fibrous tissue. This forces the heart to pump harder, which in turn elevates blood pressure. The research team concluded that fat cells lacking beige fat release certain signalling enzymes into their immediate environment, and this was sufficient to activate the genes responsible for fibrosis. One of these enzymes, named QSOX1, has previously been implicated in cancer research due to its significant role in tissue reshaping. Under healthy conditions, beige fat typically suppresses the production of QSOX1. However, when fat cells lose their beige fat characteristics, QSOX1 is rapidly produced, triggering a chain reaction that culminates in high blood pressure.

The team also highlighted the relevance of their findings to humans, noting that existing clinical cohorts show that patients with mutations in PDM16 – the gene whose loss activates QSOX1 in mice – tend to have higher blood pressure. This correlation suggests that the insights gained from mouse studies are highly applicable to human physiology. The researchers express hope that their work will pave the way for future investigations into how variations in the fat surrounding blood vessels influence where diseases are most likely to develop.

Dr. Paul Cohen, a physician-scientist specializing in obesity and metabolic disease and the study lead, commented: "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."

This discovery comes at a time when an estimated 14 million adults in the UK are living with high blood pressure, a figure that is steadily rising. While lack of exercise, poor diet, and excessive alcohol consumption have long been identified as contributors to the increase in hypertension, the risk posed by chronic stress, particularly among young people, has often been overlooked. Nearly 170,000 individuals aged 16 to 24 are estimated to be living with undiagnosed hypertension. Furthermore, the British Heart Foundation reports that of the approximately 16 million UK adults estimated to have high blood pressure, up to half are not receiving effective treatment, and as many as five million are believed to be undiagnosed.