Blood Pressure Drug Losartan Awakens Metabolic Brown Fat in Surprise Discovery

In a finding that could reshape how clinicians think about one of the most widely prescribed classes of cardiovascular medications, researchers at The Rockefeller University have discovered that losartan, a mainstay treatment for high blood pressure, appears to stimulate brown adipose tissue, the specialized fat long associated with improved metabolic and cardiovascular health. The study, published in Nature by a team led by Paul Cohen of Rockefeller’s Laboratory of Molecular Metabolism, in collaboration with Heiko Schöder and Daniel Lafontaine of Memorial Sloan Kettering Cancer Center, suggests that repurposing an established angiotensin receptor blocker with a decades-long safety record may offer a clinically viable route to activating a tissue that most adults carry only in small, dormant quantities.

Brown adipose tissue, or BAT, differs fundamentally from the white fat that stores excess energy. Packed with mitochondria, brown fat burns calories to generate heat, a process known as non-shivering thermogenesis. In humans, deposits sit in six principal regions of the body, including the neck, the armpits, and the areas surrounding organs such as the heart and kidneys. Because active brown fat consumes glucose and fatty acids, researchers have suspected for years that boosting its activity could help combat obesity, diabetes, and heart disease. What has been missing is a safe, practical pharmacological switch, and the new work points to a candidate that has been sitting in medicine cabinets all along.

The road to that candidate began with an unusually rich dataset. In 2021, Cohen’s laboratory characterized roughly 50,000 patients from Memorial Sloan Kettering Cancer Center, finding that people whose scans revealed brown fat had significantly lower odds of cardiometabolic diseases, including coronary artery disease and type II diabetes. That analysis, however, had been deliberately narrow. “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,” Cohen says. “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.”

The expanded investigation adopted what the team describes as a reverse translational approach, working backward from clinical observations to uncover the molecular mechanisms beneath them. First author Nicolás Gómez-Banoy, an endocrinologist and instructor in clinical investigation in Cohen’s laboratory, analyzed PET/CT scans from more than 100,000 patients. These imaging studies had originally been performed as part of routine cancer surveillance, but they inadvertently captured brown fat activity whenever the tissue lit up on the scans. Gómez-Banoy applied a machine learning tool developed by colleagues at MSKCC to quantify the total degree of BAT activity in each patient, along with the activity in each of the six anatomical regions where the tissue resides.

That regional breakdown proved to be one of the study’s most striking technical contributions. Location mattered, and it mattered differently depending on the disease in question. “For example, the axillary, or armpit, area was linked to a decreased risk of high blood pressure compared to other regions,” Gómez-Banoy says. Across the cohort as a whole, patients with detectable brown fat showed better glycemic parameters, healthier lipid profiles, more favorable echocardiographic indices, and lower levels of inflammatory markers than patients without it. The pattern held across diagnoses, suggesting that brown fat is not merely a bystander in metabolic health but an active participant whose influence radiates through multiple organ systems.

When the researchers cross-referenced medication histories against scan findings, a clear signal emerged: patients taking angiotensin receptor blockers had a higher presence of brown fat in their imaging. To determine whether the association was causal, the team turned to controlled laboratory experiments. In cultured brown fat cells, losartan directly increased metabolic activity, demonstrating that the drug acts on the tissue itself rather than through some indirect systemic effect. Critically, the molecular interactions through which losartan enhanced brown fat turned out to be distinct from the pathways responsible for its well-known blood pressure-lowering properties. “The fact that its different effects are mediated by different molecular pathways is advantageous, since it means we could potentially isolate them in future therapies,” Gómez-Banoy says. “That way you would be able to stimulate brown fat in people with normal blood pressure.”

The team then extended the work into living animals. Healthy mice treated with losartan exhibited a constellation of metabolic enhancements, including increased energy expenditure, elevated oxygen consumption, and greater carbon dioxide production, all while maintaining a steady body weight. That combination, burning more fuel without losing weight, hints at a rebalancing of energy metabolism rather than a simple caloric drain. For a drug already taken daily by millions of patients worldwide, the prospect of a second, metabolically beneficial mode of action is precisely the kind of repurposing opportunity that drug developers rarely encounter, because the safety profile has already been established through decades of clinical use.

Perhaps the most unexpected dimension of the study concerns the mind rather than the body. The expanded diagnostic analysis revealed a lower incidence of anxiety and depression among patients with brown fat, a connection reported for the first time in this research. “We know that metabolically healthy people tend to have 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,” Gómez-Banoy says. The relationship runs in both directions, it seems: the team found that selective serotonin reuptake inhibitors, the antidepressants most commonly prescribed for depression, had a dampening effect on brown fat activity. Whether that dampening has clinical consequences for metabolism remains an open question, but it adds a new consideration to the long list of trade-offs physicians weigh when selecting psychiatric medications.

The findings open several avenues for future research. The team plans to study the genetics of people who naturally carry high levels of brown fat, to probe the mechanisms linking BAT to anxiety and depression, and to investigate potential downsides, including higher rates of osteoporosis and skin diseases observed in people with the tissue. Beyond losartan, the massive cohort analysis flagged numerous other medications associated with brown fat activity, some of which may prove even more potent or more selective stimulators of the tissue. “There were plenty of other medications associated with brown fat activity in our large cohort,” Cohen notes. “This is just a start.”

For now, the study stands as a compelling example of what large-scale analysis of incidental clinical data can reveal. More than 100,000 cancer surveillance scans, collected for entirely different reasons, became a window into human metabolism when paired with machine learning and a willingness to ask broad questions. The result is a hypothesis with immediate translational appeal: a drug that is cheap, widely available, and already proven safe may quietly be doing more than lowering blood pressure. Confirming that promise will require prospective clinical trials in diverse populations, but the idea that the path to healthier metabolism might run through the pharmacy’s oldest shelves is exactly the kind of surprise that keeps metabolic science, and its growing audience, watching closely.

Subject of Research: Repurposing the angiotensin receptor blocker losartan to stimulate brown adipose tissue and improve metabolic health

Article Title: Researchers discover a commonly prescribed blood-pressure drug may stimulate “healthy” brown fat

Article References: Researchers discover a commonly prescribed blood-pressure drug may stimulate “healthy” brown fat. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: brown fat, losartan, brown adipose tissue, metabolism, angiotensin receptor blockers, hypertension, PET/CT imaging, machine learning, anxiety, depression, energy expenditure, drug repurposing