Large study finds 'strong evidence' brown fat may protect against numerous chronic diseases

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A study among over 52,000 participants, published in Nature Medicine, found those who had detectable brown fat were less likely than their peers to suffer cardiac and metabolic conditions ranging from type 2 diabetes to coronary artery disease.

Unlike white fat, which stores calories, brown fat burns energy and scientists hope it may hold the key to new obesity treatments. But it has long been unclear whether people with ample brown fat truly enjoy better health. For one thing, it has been hard to even identify such individuals since brown fat is hidden deep inside the body.

The study, by far the largest of its kind in humans, confirms and expands the health benefits of brown fat suggested by previous studies. "For the first time, it reveals a link to lower risk of certain conditions," says Dr Paul Cohen, the Albert Resnick 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."

Although brown fat has been studied for decades in newborns and animals, it was only in 2009 that scientists appreciated it can also be also found in some adults, typically around the neck and shoulders. From then on, researchers have scrambled to study the elusive fat cells, which possess the power to burn calories to produce heat in cold conditions.

Large-scale studies of brown fat, however, have been practically impossible because this tissue shows up only on PET scans, a special type of medical imaging. "These scans are expensive, but more importantly, they use radiation," says 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."

A physician-scientist, Becher came up with an alternative. Right across the street from his lab, many thousands of people visit Memorial Sloan Kettering Cancer Centre each year to 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 tumour. "We realised this could be a valuable resource to get us started with looking at brown fat at a population scale," Becher says.

In collaboration with Heiko Schoder and Andreas Wibmer at Memorial Sloan Kettering, the researchers reviewed 130,000 PET scans from more than 52,000 patients, and found the presence of brown fat in nearly 10% of individuals. (Cohen notes 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).

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% had abnormal cholesterol, compared to 22.2% in those without brown fat.

Moreover, the study revealed three more conditions for which people with brown fat have lower risk: hypertension, congestive heart failure, and coronary artery disease – links that had not been observed in previous studies.

Another surprising finding was that brown fat may mitigate the negative health effects of obesity. 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 says.

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 mysterious in other conditions like 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 signalling to other organs," Cohen says.

The team plans to further study the biology of brown fat, including by looking for genetic variants that may explain why some people have more of it than others – potential first steps toward developing pharmacological ways to stimulate brown fat activity to treat obesity and related conditions.

"The natural question that everybody has is, 'What can I do to get more brown fat?'" Cohen says. "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."

 

Study Details

Brown adipose tissue is associated with cardiometabolic health

Tobias Becher, Srikanth Palanisamy, Daniel J Kramer, Mahmoud Eljalby, Sarah J Marx, Andreas G Wibmer, Scott D Butler, Caroline S Jiang, Roger Vaughan, Heiko Schöder, Allyn Mark, Paul Cohen

Published in Nature Medicine on 4 January 2021

Abstract
White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear1,2. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron emission tomography–computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. 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. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. 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. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health.

 

Rockefeller University material

 

Nature Medicine study (Open access)

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