Summary
A bioRxiv preprint reports that activating perivascular thermogenic fat improved aortic stenosis in mice. In human PET-CT scans, thermogenic-fat activity was inversely correlated with measures of disease severity.
A bioRxiv preprint reports that stimulating thermogenic fat surrounding the aorta improved aortic stenosis in mice. Cold exposure also produced a protective effect in the mouse model, while human PET-CT imaging found that greater activity in mediastinal thermogenic fat was associated with less severe disease. The results point to a possible role for this tissue in aortic remodelling, but the human finding is a correlation, not a treatment test.
Perivascular adipose tissue (PVAT) is the fat layer around blood vessels. In the thoracic region, it has features of thermogenic fat, which dissipates energy and releases signalling molecules. Aortic stenosis is a narrowing of the aortic valve that obstructs blood flow from the heart.
What the mouse experiments found
The researchers studied a mouse model of aortic stenosis, using a β3-adrenergic agonist and cold exposure to stimulate thermogenic fat. They also used genetically modified mice with deficient PVAT development to assess whether the tissue was involved in the effects.
Pharmacological activation improved aortic stenosis in mice with PVAT, but not in mice deficient in PVAT development. Cold exposure was also protective against stenosis in the model. Together, these results support a role for PVAT in the response to thermogenic stimulation.
The team observed increased aortic distensibility—the ability of the aorta to expand—and cellular remodelling of the aortic wall after PVAT activation. The authors propose that polyunsaturated fatty acids and oxylipins released by perivascular fat cells may contribute to these changes. That mechanism is presented as a possible explanation, rather than a settled account of how the effect occurs.
Human imaging adds an association
The researchers used 18F-FDG PET-CT imaging to examine thermogenic-fat activity in people with aortic stenosis. Higher activity in mediastinal thermogenic fat was negatively correlated with diagnostic criteria for disease severity: greater activity was associated with less severe stenosis.
This human result is consistent with the mouse findings, but imaging correlation cannot show that activating the tissue would reduce stenosis in people. The interventions were tested in mice; the human analysis measured an association. The work is a bioRxiv preprint and has not yet undergone peer review.
The findings identify PVAT as a potential contributor to aortic-wall remodelling and a candidate for further study as a way to influence disease progression. They do not yet establish a treatment for patients. Testing whether the pathway can be safely and effectively targeted in people would require further research.