- There are several causes for high blood pressure, including obesity.
- People who have obesity generally have more white fat, which stores energy, than beige fat, which burns calories.
- A new study has found that beige fat may actually help regulate blood pressure, as observed in a mouse model.
There are several causes for high blood pressure. Some factors, like age, ethnicity, and genetics, are non-modifiable, while others, like diet, physical activity level, stress, smoking, and obesity, are modifiable risk factors.
People who have obesity generally have more white fat — known as white adipose tissue — in the body than beige fat, or brown adipose tissue. White fat stores calories for energy, while beige fat is functional and helps to burn calories.
Now, a new study recently published in the journal Sciencehas found that beige fat may actually help control blood pressure, via a mouse model.
For this study, researchers used a mouse model in which the mice were genetically altered so they could not form beige fat. They did this by removing the Prdm16 gene from fat cells in the mice.
“When we talk about fat, most people think about the classical white fat located in our subcutaneous and visceral fat depots, which enlarge substantially during obesity,” Mascha Koenen, PhD, Charles H. Revson Postdoctoral Fellow in the Laboratory of Molecular Metabolism at The Rockefeller University in New York and first author of this study, explained to Medical News Today. “The functional unit of these depots is the white adipocyte, which stores excess energy in the form of lipids.”
“In addition to this well-known fat tissue, we also have another type of adipose tissue, which is called thermogenic or heat-producing fat,” Koenen continued.
“Thermogenic fat includes brown and beige adipocytes, which in contrast to white adipocytes, burn energy to produce heat when activated. Cold stimulation is a classical activator of these cells, and
our lab has shown that humans with thermogenic fat have a lower prevalence of cardiovascular and metabolic diseases, including hypertension and diabetes.”
— Mascha Koenen, PhD
“We focused specifically on mouse beige fat since previous studies have shown a strong resemblance to thermogenic fat in adult humans. Since not all humans have detectable thermogenic fat in the absence of stimulation, we wanted to understand the underlying beneficial molecular link between thermogenic fat and blood pressure regulation,” Koenen added.
At the study’s conclusion, researchers found that in the mice engineered not to create beige fat, they began to express the markers of white fat, including angiotensinogen — an inactive protein mostly produced by the liver that is the precursor for a hormone known to increase blood pressure.
Scientists found that the fat wrapping around blood vessels in the mice included white fat markers, such as angiotensinogen. Researchers reported these mice experienced elevated blood pressure and mean arterial pressure, as well as stiff, fibrous tissue beginning to collect around the vessels.
“In our previous study, we found that individuals lacking thermogenic fat in humans have an increased prevalence of hypertension compared with individuals with active thermogenic fat,” Paul Cohen, MD, PhD, Albert Resnick, MD Associate Professor, and head of the Weslie R. and William H. Janeway Laboratory of Molecular Metabolism at The Rockefeller University in New York, and senior author of this study, explained to MNT.
“Whether this observation represented a causal relationship and, if so, what the molecular mechanism might be, were unclear,” he said.
“We used a reverse translational approach to model this observation from humans in mouse models, by using mice that lack beige adipocyte identity due to loss of PRDM16 in adipocytes,” Cohen continued. “In our model, we specifically genetically modified only adipocytes, but discovered an impact on the vasculature, suggesting a crosstalk between adipose tissue and the vasculature.”
“Indeed, loss of PRDM16 in adipocytes leads to increased sensitivity to ANGII (a prominent
Additionally, researchers were able to identify a specific enzyme called QSOX1, which beige fat naturally helps turn off. However, when QSOX1 is overproduced, it can lead to hypertension.
“We identified QSOX1 as an enzyme that is directly negatively regulated by (the gene) PRDM16 in adipocytes and that is secreted,” Koenen said. “In our study, we showed that QSOX1 is dramatically upregulated when Prdm16 is deleted in adipocytes.”
“When we prevent this upregulation through deletion of both Prdm16 and Qsox1 in adipocytes we prevent the fibrotic remodeling of the vasculature and its hypersensitivity to ANGII. Since QSOX1 is an enzyme, it could represent a new therapeutic target for blood pressure regulation in individuals lacking thermogenic fat.”
— Mascha Koenen, PhD
“Going forward, we are very interested in understanding how QSOX1 regulates vascular fibrosis and function,” Cohen added. “We are also excited to explore whether and how thermogenic fat might influence other cardiovascular pathology.”
MNT spoke with Cheng-Han Chen, MD, a board certified interventional cardiologist and medical director of the Structural Heart Program at Saddleback Medical Center in Laguna Hills, CA, about this study.
“This study used a genetically modified mouse model and found that mice having a different ‘type’ of stored fat in their body can have blood vessels that are more prone to developing high blood pressure,” Chen explained. “These results build on our evolving understanding of how fat tissue influences our other organs, and provide potential future areas for research into possible therapies to reduce the risk of high blood pressure.”
“High blood pressure is one of the most prevalent and serious risk factors for many significant medical conditions, including heart disease and stroke. Developing new and better ways to regulate high blood pressure will go a long way towards helping us reduce the major burden of this condition on our society.”
— Cheng-Han Chen, MD
“Future research could investigate whether the molecular mechanism identified in this mouse model also plays a significant role in human biology, and whether a drug targeting this mechanism could potentially play a role in controlling blood pressure,” Chen added.