Home Cardiovascular Disease Brown Fat in Humans Linked with Improved Cardiometabolic Health

Brown Fat in Humans Linked with Improved Cardiometabolic Health

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heart model

The results of research headed by a team at The Rockefeller University has found that people who carry detectable brown fat in their bodies are at a reduced risk of cardiac and metabolic disorders, including type 2 diabetes mellitus (T2DM) and coronary artery disease. The study, through which the team analyzed positron emission tomography (PET) scans from more than 52,000 people, is claimed to be by far the largest of its kind in humans, and confirms and expands on evidence for the health benefits of brown fat that has been suggested by previous studies. “For the first time, it reveals a link to lower risk of certain conditions,” said Paul Cohen, the Albert Resnick, MD, Assistant Professor and senior attending physician at The Rockefeller University Hospital. “These findings make us more confident about the potential of targeting brown fat for therapeutic benefit.”

Resnick and colleagues report on their findings in Nature Medicine, in a paper titled, “Brown adipose tissue is associated with cardiometabolic health,” in which they concluded, “Our study indicates an important contribution of BAT to cardiometabolic health and suggests that BAT has therapeutic potential in humans.”

Brown fat—or brown adipose tissue; BAT—is the type of tissue that you would want more of, the researchers suggested. Unlike white fat (white adipose tissue; WAT), which stores calories, brown fat burns energy which is dissipated as heat, and scientists hope that it may hold the key to new obesity treatments.

Although brown fat has been studied for decades in newborns and in animals, it was only in 2009 that scientists appreciated that BAT can also be also found in some adults, typically around the neck and shoulders. “In 2009, a series of papers confirmed the presence of active BAT in adults, which correlated with lower body mass index (BMI), decreased age, colder outdoor temperature, female sex and decreased glucose levels,” the authors noted. Since then, researchers have scrambled to study these elusive fat cells, which possess the power to burn calories to produce heat in cold conditions.

However, it has long been unclear whether people with ample brown fat enjoy better health. Small studies in healthy humans have shown that cold-activated BAT is associated with increased energy expenditure—among other metabolic effects—which has “generated enthusiasm for BAT as a therapeutic target for obesity and associated diseases,” the authors noted. However, they acknowledged, “… these studies have been too small to definitively address whether BAT is a clinically meaningful modulator of metabolic and cardiovascular disease in humans.”

In these PET scans, the person on the left has abundant brown fat around the neck and cervical spine. The person on the right has no detectable brown fat. [MSKCC radiologists Andreas G. Wibmer and Heiko Schöder]
Even identifying individuals who carry brown fat is difficult, since the tissue is hidden deep inside the body. This means that large-scale studies of brown fat have been practically impossible, because the tissue shows up only on positron emission tomography (PET) scans. “These scans are expensive, but more importantly, they use radiation,” said Tobias Becher, the study’s first author and formerly a Clinical Scholar in Cohen’s lab. “We don’t want to subject many healthy people to that.”

 

Becher, who is a physician-scientist, came up with an alternative. His lab is right across the street from the Memorial Sloan Kettering Cancer Center, where each year many thousands of people undergo PET scans for cancer evaluation. Becher knew that when radiologists detect brown fat on these scans, they routinely make note of it to make sure it is not mistaken for a tumor. “We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Becher noted.

In collaboration with Heiko Schoder and Andreas Wibmer at Memorial Sloan Kettering, the researchers reviewed 130,000 PET scans from 52,487 patients, and found the presence of brown fat in nearly 10% of individuals. Cohen suggested that this figure is likely an underestimate, because the patients had been instructed to avoid cold exposure, exercise, and caffeine, all of which are thought to increase brown fat activity.

When the investigators analyzed the data, they found that several common and chronic diseases were less prevalent among people with detectable brown fat. For example, only 4.6% had type 2 diabetes, compared with 9.5% of people who did not have detectable brown fat. Similarly, 18.9% of individuals who carried brown fat had abnormal cholesterol, compared with 22.2% of those without brown fat.

The study in addition revealed that people with brown fat also had lower risk of hypertension, congestive heart failure, and coronary artery disease. These links had not been observed in previous studies. “We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension,” they wrote in their paper.

Another surprising finding was that brown fat may reduce the negative health effects of obesity.” The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity,” they further stated. In general, obese people have increased risk of heart and metabolic conditions; but the researchers found that among obese people who have brown fat, the prevalence of these conditions was similar to that of non-obese people. “It almost seems like they are protected from the harmful effects of white fat,” Cohen said. “While obesity is generally associated with decreased BAT function, obese individuals who retain BAT activity appear to be protected against conditions linked to excess adiposity,” the investigators further commented.

The actual mechanisms by which brown fat may contribute to better health are still unclear, but there are some clues. For example, brown fat cells consume glucose in order to burn calories, and it’s possible that this lowers blood glucose levels, a major risk factor for developing diabetes.

The role of brown fat is more enigmatic in other conditions, such as hypertension, which is tightly connected to the hormonal system. “We are considering the possibility that brown fat tissue does more than consume glucose and burn calories, and perhaps actually participates in hormonal signaling to other organs,” Cohen added.

The team plans to further study the biology of brown fat, and will look for genetic variants that may explain why some people have more of the tissue than others. This knowledge could potentially represent the first steps towards developing drugs that stimulate brown fat activity as an approach to treating obesity and related conditions. “ … variability in BAT prevalence and activity suggests a possible genetic determinant of its biology,” the authors explained. “Consistent with this, our understanding of genetics as a contributor to T2DM development has evolved substantially. It is possible then that genetic factors contributing to BAT development and activity may affect the pathogenesis of T2DM and metabolic syndrome.”

Cohen further pointed out, “The natural question that everybody has is, ‘What can I do to get more brown fat?’ We don’t have a good answer to that yet, but it will be an exciting space for scientists to explore in the upcoming years.”

And as the authors concluded, “As the global obesity crisis worsens despite considerable efforts to improve prevention and treatments, the emergence of BAT as a potential therapeutic target is appealing. Future research should aim to improve our understanding of BAT regulation in humans and to develop mechanisms to safely modulate BAT activity.”