Converting white fat to brown reduces high blood pressure in mice

Researchers have converted white fat to brown fat, known for its ability to relax blood vessels, in mice to reduce high blood pressure. They say their findings pave the way for targeted treatments for high blood pressure and other metabolic disorders such as obesity and type 2 diabetes.

High blood pressure, or hypertension, is a leading cause of cardiovascular disease and premature death worldwide. The World Health Organization (WHO) estimates that 1.28 billion adults aged 30 to 79 have hypertension, with around half (46%) unaware they have the condition.

An important regulator of blood vessel (vascular) tone and, therefore, blood pressure is perivascular adipose tissue (PVAT), the fat deposited around the blood vessels that releases factors controlling contraction and relaxation. PVAT in the resistance arteries that regulate the pressure and flow of blood is characterized as white adipose tissue or WAT. In patients with obesity, diabetes, and hypertension, it’s common to see inflammation of this tissue.

Brown adipose tissue (BAT), or ‘brown fat,’ on the other hand, has been shown to have a stronger anticontractile effect on resistance vessels, working in a way that’s mechanically different to WAT. It’s known that WAT can be converted into beige adipose tissue, similar in morphology to BAT, in a process called ‘browning.’ In a new study, researchers investigated whether inducing brown fat controls hypertension in mice.

The researchers induced browning in male mice by administering a beta-3 agonist, angiotensin II (ANG II), or a combination of the two. A control group received only saline. Beta-3 agonists activate beta-3 receptors on muscle cell membranes, causing relaxation, whereas ANG II causes vascular constriction. The animals’ blood pressure and vascular function were measured at baseline and on day seven of the treatment.

The researchers found that the anticontractile effect of PVAT was lost in the untreated hypertensive mice, who showed an increase in vascular tone and blood pressure. Browning of PVAT maintained the tissue’s anticontractile effect, improved endothelial function, and reduced the development of hypertension. The endothelium, the inner cellular lining of the blood vessels, is a major player in controlling vascular tone.

“The data from the present study demonstrate that dysfunctional PVAT occurs in hypertension,” said the researchers. “However, a phenotypic switch from white to a beige phenotype is protective of PVAT function and therefore reduces vascular contraction and protects endothelial function. Consequently, browning of PVAT results in reduced development of hypertension.”

While not establishing a causal link between PVAT and hypertension, the researchers consider their findings important.

“Although a causal relationship between PVAT and hypertension is not clearly demonstrated these studies lend strong support to PVAT dysfunction as a pivotal mechanism in the development of vascular dysfunction and subsequently hypertension,” the researchers said.

They say their research could pave the way for developing targeted treatments that protect PVAT, which would not only assist people with hypertension but also those with conditions marked by PVAT dysfunction.

“Importantly, PVAT dysfunction occurs not only in hypertension but also in metabolic disorders such as obesity and type 2 diabetes mellitus, and the potential patient population that may benefit from a treatment targeted toward the protection [of] PVAT is large.”

The study was published in the American Journal of Physiology.