Researchers have found that losartan, a commonly prescribed blood pressure medication, may stimulate healthy brown fat activity, potentially leading to improved metabolic and psychiatric health.
New research from Rockefeller University has revealed that losartan, an angiotensin receptor blocker (ARB) widely used to treat high blood pressure, enhances the activity of brown adipose tissue (BAT) in mice. This discovery suggests that repurposing losartan could serve as a clinical strategy to stimulate brown fat, which has previously been linked to improved cardiovascular health and, for the first time, psychiatric health.
The study, published in the journal Nature, was conducted by a team led by Paul Cohen, head of the Laboratory of Molecular Metabolism at Rockefeller University, alongside researchers from Memorial Sloan Kettering Cancer Center (MSKCC), including Heiko Schöder and Daniel Lafontaine. Their findings indicate that individuals with more brown fat tend to have a lower prevalence of various health conditions.
The researchers initially identified the connection between brown fat and ARBs through an analysis of medical records from over 100,000 patients at MSKCC. This analysis builds on previous work conducted by Cohen’s lab in 2021, which characterized approximately 50,000 patients. In that earlier study, it was found that patients with higher levels of brown fat exhibited significantly lower risks of cardiometabolic diseases, such as coronary artery disease and type II 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,” Cohen stated. “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.”
Methodology and Findings
The current research employed a reverse translational approach, a method that aims to uncover the biochemical mechanisms behind clinical observations. The team analyzed PET/CT scans from over 100,000 patients, which were part of routine cancer surveillance. They specifically focused on scans that detected the existence of brown fat, located in six regions of the body, including the neck, armpit, and surrounding organs such as the heart and kidneys.
Nicolás Gómez-Banoy, the study’s first author and an endocrinologist in Cohen’s lab, utilized machine learning tools developed by MSKCC colleagues to quantify the total activity of brown fat in each patient, as well as in each of the six anatomical regions. The study found that the location of brown fat is crucial; for instance, higher activity in the axillary area was associated with a decreased risk of high blood pressure compared to other regions.
“But overall, patients with brown fat have better glycemic parameters, lipid profiles, and echocardiographic indices, as well as lower inflammatory markers,” Gómez-Banoy noted.
Further analysis revealed that patients taking ARBs exhibited a higher presence of brown fat in their scans. To further explore this relationship, the researchers conducted experiments testing the effects of losartan on cultured brown fat cells, demonstrating that the drug directly increased metabolic activity. They found that the mechanisms through which losartan induces these effects differ from those responsible for its well-known ability to lower blood pressure.
“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 explained. “That way you would be able to stimulate brown fat in people with normal blood pressure.”
Implications for Mental Health
In addition to its metabolic benefits, the team uncovered potential connections between brown fat and mental health. Their analysis indicated a lower incidence of anxiety and depression among patients with brown fat. “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 stated. Conversely, the study found that selective serotonin reuptake inhibitors (SSRIs), commonly prescribed for depression, had a suppressive effect on brown fat activity.
The findings from this study open several new avenues for research, including investigations into the genetics of individuals with high levels of brown fat, the relationship with anxiety and depression, and potential adverse effects, such as increased rates of osteoporosis and skin diseases among those with brown fat. Researchers also noted that there are other medications beyond losartan that may warrant investigation for their association with brown fat activity.
“There were plenty of other medications associated with brown fat activity in our large cohort,” Cohen remarked. “This is just a start.”
