A Common Blood Pressure Pill Could One Day Help Switch On Healthy Brown Fat

A cancer scan looks for a tumor and records plenty else on the way. A team led by Paul Cohen of the Rockefeller University went back through 101,243 PET-CT scans from patients at Memorial Sloan Kettering Cancer Center. The scans were taken for cancer care. Sitting in them was brown fat, the kind of fat that burns energy to make heat instead of storing it.

Their study, published October 14 in Nature, found that across all diagnoses, heart disease and psychiatric illness were less common in people whose scans showed brown fat. Then came a surprise from the medicine cabinet. People taking a family of blood pressure drugs called angiotensin receptor blockers were more likely to have brown fat, and one of them, losartan, switched brown fat cells on in the lab and raised energy use in mice.

Where the machine learning came in

Brown fat is not the soft layer around the belly. As Nature’s news team explains, it sits mostly around the neck, armpits and chest, and it shows up on PET-CT scans because it soaks up a radioactive form of glucose when it is active.

Whether a person counted as having brown fat came from what was reported on their scans, not from software. Measuring how much of it is working, and where, is harder. For that the team used a machine learning tool called TriDFusion (3DF), built on an nnU-net image model by colleagues at Memorial Sloan Kettering, to outline brown fat and measure its activity, in total and spot by spot, in 8,709 patients, nearly all of the 8,897 people with brown fat in the cohort. The authors write that this let them do so rapidly, and ask a sharper question: does more active brown fat, in one spot, go with better health?

The tool’s role is specific. The links to heart disease, mental health and blood pressure drugs rest on whether brown fat was present. The measurements behind “more is better” below came from the machine learning.

What the scans showed

• More is better. Higher brown fat activity, especially in the armpit, went with lower odds of cardiometabolic disease and a healthier spread of white fat.
• The whole body looked healthier. People with brown fat had better blood sugar measures, lipid profiles, inflammation markers and heart ultrasound readings.
• The mind may be part of it. Anxiety and depression were less common in people with brown fat, a link the authors say had not been described before.

The team screened 511 diagnosis codes. Of 104 they examined closely, 98 held up after adjusting for other factors, and 92 of those were less common in people with brown fat.

From a pattern to a pill

Losartan users were more likely to have brown fat (odds ratio 1.36), and valsartan users too (1.52). In cultured brown fat cells, losartan at higher doses raised UCP1, the main heat-making protein, about as much as noradrenaline did. In mice it raised whole-body energy use while body weight held steady. In cells, the team tied the effect to a pathway called PPARγ rather than to the receptor the drug blocks to lower blood pressure. First author Nicolás Gómez-Banoy said in a Rockefeller University release that this could one day let a therapy stimulate brown fat in people with normal blood pressure.

Shingo Kajimura of Harvard Medical School told Nature:

“This is one of the most comprehensive and, probably, significant works in the field.” Shingo Kajimura, Harvard Medical School, via Nature

Irfan Lodhi of Washington University in St. Louis added that because the study looks backward, more work is needed to prove brown fat causes the benefits. The patients were all at a cancer center, and scans taken without cold exposure can miss brown fat.

Losartan has not been tested for brown fat in people, so it is no reason to start taking it. What the study offers is a map: for people living with diabetes, heart disease or depression, it points researchers toward an old, familiar drug, and toward others. As Cohen said in a Rockefeller University release, plenty of other medications were linked to brown fat in the cohort. “This is just a start.”