Brown Fat May Protect Against Diabetes and Obesity in Humans

Marlene Busko

July 28, 2014

A new study in 12 men with and without brown fat has shown for the first time that when activated by mild exposure to cold, brown fat increases blood glucose disposal, insulin sensitivity, and energy expenditure in humans.

If confirmed and if future research identifies safe and efficacious lifestyle or pharmaceutical interventions to activate brown fat or induce "browning" of more abundant white fat, "brown adipose issue will likely emerge as a therapeutic target in the battle against obesity and diabetes," according to the researchers.

Specifically, the work showed that following several hours of exposure to mild cold, the resting energy expenditure — the number of calories a person would burn in 24 hours if they were at rest — in the men with brown fat increased by 15% compared with when they were in a comfortable ambient temperature. In addition, their glucose metabolism was revved up, such that if brown fat remained activated, it would burn up 23 g of glucose in 24 hours.

"We have shown a physiologically, clinically significant effect of brown fat on whole-body glucose homeostasis, and this means that brown fat may function as an antiobesity and antidiabetic tissue in humans...[which] is great news," senior author Labros S. Sidossis, MD, of the University of Texas, in Galveston, told Medscape Medical News. If confirmed, this research hints that keeping ambient room temperature closer to 70°F for even a couple of hours might have significant effects on blood glucose regulation, he said.

The study was published online July 23 in Diabetes.

Investigating Glucose Homeostasis, Insulin Resistance

"Until a few years ago, we thought that brown fat existed only in animals and in humans only in babies," Dr. Sidossis explained. In 2009, three papers published in the New England Journal of Medicine reported that some adults had small pockets of brown fat — which is brown because of mitochondrial content — in supraclavicular and abdominal areas. People in their 60s, 70s, and 80s and very obese people have less brown fat or none at all, Dr. Sidossis noted.

Retrospective studies have shown that thin people were more likely to have brown fat than obese people, but it was not clear how brown fat affected whole-body glucose homeostasis and insulin sensitivity.

 
This paper says cold will 'turn on' brown fat and cold will change the hormones that regulate body weight, but it doesn't give you that next step that says sleeping in the cold will make you a fashion model."
 

To investigate this, the researchers enrolled 12 healthy men. In the first part of the study, the men were exposed to 5 to 8 hours of mild cold (1°C above the temperature where subjects were shivering). They were then injected with radioactive glucose and had a positron-emission tomography/computed tomography (PET/CT) scan, which revealed whether they had brown adipose tissue.

This identified 7 men who were positive for brown fat (with a mean volume of 69 mL of brown fat) and 5 men who were deemed negative (with a mean volume of 4 mL of brown fat).

Other than brown fat, the men in the 2 groups were similar. They had a mean age of around 45, a mean body mass index (BMI) around 29, and about 31% body fat.

In the second part of the study, the men were tested under a comfortable room temperature.

In both parts of the study, the researchers collected blood and breath samples to observe changes in glucose, insulin, and hormone levels and rates of oxygen consumption and carbon-dioxide production. They also aspirated brown- and white-fat tissue samples to analyze in cellular energy production and gene expression in a subset of the men.

The observed changes occurred only after cold exposure, not normal-temperature exposure, and only in the group of men with brown fat.

"This study was the first time that it was shown that when you compare men who have brown fat with another group of men who don't have brown fat, people with brown fat consume significant amounts of blood sugar," Dr. Sidossis said. "Now, the thing is to make sure or to find ways to activate this tissue."

The researchers expect to soon publish a related study investigating white fat and beige fat.

"Important Translational Science," More Study Needed

Steven Smith, MD, of the Sanford-Burnham Medical Research Institute in Winter Park, Florida, agrees that this research looks promising but is also cautious. "This paper says cold will 'turn on' brown fat and cold will change the hormones that regulate body weight, but it doesn't give you that next step that says sleeping in the cold will make you a fashion model," he commented.

However, after about 50 years of study in rats, "the human clinical data are just at the point where I think we need to get serious about trying to understand if there are clinical implications of what turns out to be important translational science," he added.

One intriguing finding was the increase in hormones such as norepinephrine after cold exposure in the men who had brown fat. "I think it is really interesting that sleeping in the cold can change your hormones....By and large these were beneficial effects on hormones that we recognize are important for metabolism," he noted.

Dr. Sidossis has reported no relevant financial relationships. Disclosures for the coauthors are listed in the article. Dr. Smith has served as a director, officer, partner, employee, advisor, consultant, or trustee for Amylin Pharmaceuticals, Takeda, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Elcelyx, Eli Lilly, Five Prime Therapeutics, GlaxoSmithKline/Genpact, NGM Pharma, Novo Nordisk, Orexigen Therapeutics, Piramal Life Sciences, Takeda Global Research and Development, and Zafgen. He has received research grants from Amylin Pharmaceuticals, Eli Lilly, and Takeda, and he holds stock in Jenrin Discovery and Zafgen.

Diabetes. Published online July 23, 2014. Abstract

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