Blood pressure drug losartan boosts metabolism by stimulating brown fat

Losartan, a drug commonly prescribed for high blood pressure, boosts brown adipose tissue or "brown fat" activity and enhances its metabolism, according to a preclinical study by Weill Cornell Medicine, Rockefeller University and Memorial Sloan Kettering Cancer Center researchers. The findings suggest that repurposing losartan—an angiotensin receptor blocker (ARB) with a well-known safety profile—may potentially offer a therapeutic approach to stimulate brown fat, which has been linked to improved cardiovascular health. Unlike normal white fat, which stores energy in the body, brown fat burns calories to generate heat. The study also reported, for the first time, that brown fat is associated with reduced prevalence of psychiatric diseases.

The study, published Oct. 14 in Nature, analyzed PET/CT scans that were performed as part of cancer surveillance for over 100,000 patients. The researchers focused on the scans that detected brown fat, which is located in six regions of the body, including the neck, armpit and around organs like the heart and kidneys.

The current study builds on discoveries by senior author Dr. Paul Cohen, Albert Resnick, M.D. Associate Professor and physician at The Rockefeller University. His lab found that people with brown fat had significantly lower odds of cardiometabolic diseases, including coronary artery disease and type 2 diabetes.

We only looked for a few diagnostic codes in that study, mainly focusing on cardiovascular disease since that's what this tissue has historically been associated with. The scope of this new analysis is far more expansive. We doubled our number of patients and considered more than 500 codes, which allowed us to unearth many new insights."

Dr. Paul Cohen, Rockefeller University

First author Dr. Nicolás Gómez-Banoy, an endocrinologist and instructor in clinical investigation in Dr. Cohen's lab and a fellow in medicine in the Comprehensive Weight Control Center and Division of Endocrinology, Diabetes and Metabolism at Weill Cornell, quantified the total activity of brown fat in each patient, as well as the activity in each of the six anatomical regions.

Dr. Gómez-Banoy found that, in addition to having brown fat, the location of this tissue was important, since higher brown fat activity in certain regions seemed to have greater influence on specific diseases.

"For example, the axillary, or armpit, area was linked to a decreased risk of high blood pressure compared to other regions," said Dr. Gómez-Banoy, who is also a graduate of the Tri-I Medical Research Track (MRT) program. "But overall, patients with brown fat have better glycemic parameters, lipid profiles and echocardiographic indices, as well as lower inflammatory markers."

Further analyses revealed that patients taking ARBs had more brown fat in their scans. To investigate this relationship, the researchers tested how losartan affected cultured brown fat cells and observed that the drug directly increased metabolic activity in the cells. They also learned that losartan used different molecular mechanisms to impact brown fat metabolism versus to lower blood pressure.

"The fact that different molecular pathways mediate its different effects is advantageous, since it means we could potentially isolate them in future therapies," Dr. Gómez-Banoy said. "That way you would be able to stimulate brown fat in people with normal blood pressure."

Healthy mice treated with losartan also showed many indicators of enhanced metabolism, such as increased energy expenditure, oxygen consumption and carbon dioxide production, while maintaining a steady body weight.

The team also uncovered links to mental health, including a lower incidence of anxiety and depression in patients with brown fat. "We know that metabolically healthy people tend to have a lower incidence of psychiatric diseases, so it could be that having brown fat makes you more metabolically healthy, and this correlates with fewer psychiatric issues," Dr. Gómez-Banoy said. Conversely, they found that SSRIs, commonly prescribed for depression, had a dampening effect on brown fat activity.

The findings open several new research paths, such as exploring drugs beyond losartan, studying the genetics of people with higher brown fat levels and understanding the connection to anxiety and depression.

"There were plenty of other medications associated with brown fat activity in our large cohort," Dr. Cohen said. "This is just a start."