Beige fat surrounding blood vessels actively works to keep high blood pressure in check, according to a new study in mice, promoting healthy vascular function even during obesity. The findings support the notion that therapeutic activation of thermogenic fat tissue could help reduce the risk of cardiovascular disease. High blood pressure is a leading cause of heart disease and stroke and is a major risk factor for early death. Adipose tissue, or fat, plays an active role in regulating blood pressure. However, growing evidence suggests that it's the type of fat, not simply the amount, that seems to matter most. While excess white fat is linked to higher blood pressure, brown and beige fat – best known for their role in producing metabolic heat – is associated with a lower risk of hypertension, even in obesity. Beige perivascular adipose tissue (PVAT) surrounds blood vessels and has features of both white and brown fat. Yet, despite these observations, it has been difficult to disentangle the specific roles of different fat types and determine the mechanisms linking adipose biology and blood pressure regulation.
Using mice genetically engineered to lack functional beige fat tissue, Masha Koenen and colleagues show that beige PVAT supports healthy blood vessels and blood pressure control. According to the findings, mice lacking the protein PRDM16 – a major gene expression regulator of the adipose beiging process – showed extensive remodeling of perivascular adipose tissue, increased vasoconstriction and vascular fibrosis, and increased blood pressure, even without obesity. Koenen et al. show that loss of Prdm16 depressed the circulating enzyme QSOX1 and that deleting Qsox1 in Prdm16-deficient mice prevented vascular fibrosis, normalized vascular function, and reduced blood pressure. Moreover, in a meta-analysis of genome-wide association studies that used data from three biobanks, the authors found that human PRDM16 variants were associated with higher blood pressure. "Koenen et al.'s findings suggest that the activation of brown adipose tissue by boosting or stabilizing PRDM16 expression could have cardiovascular benefits," write Mandy Grootaert and Aernout Luttun in a related Perspective. "Although current human and nonhuman data are encouraging, well-controlled clinical trials are needed to determine whether triggering beiging of adipose tissue reduces the frequency of adverse cardiovascular events in patients."
