Brown Adipose Tissue: A Really Cool Idea
Abstract & commentary
By Barbara A. Phillips, MD, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a retained consultant for Cephalon and Ventus; and serves on the speakers bureau for Cephalon and Boehringer Ingelheim.
Synopsis: Brown adipose tissue is involved in temperature regulation, and relates to metabolic rate and body mass index. Its activity appears to be reduced in people who are obese.
Source: van Marken Lichtenbelt WD, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009; 360:1500-1508.
These authors sought to learn more about the amount and function of brown adipose tissue in healthy people. They were interested in this because data from animal studies have showed that brown adipose tissue may be thermogenic (heat-generating) in response to cold environments. The mechanism of this heat generation is believed to be mediated through uncoupling protein 1 (UCPI 1), which uncouples mitochondrial respiration from ATP production to dissipate energy. Further, some work has suggested that the brown adipose tissue may relate to body mass index (BMI). Little is known about the amount, distribution, and weight-modifying effects (if any) of brown adipose tissue in adult humans. These investigators set out to examine the presence, distribution, and activity of brown adipose tissue in healthy volunteers in relation to body composition and energy metabolism.
The authors recruited 24 healthy male volunteers (10 lean, BMI < 25 kg/m2; 14 overweight or obese, BMI ≥ 25 kg/m2). These scientists used positive emission tomography (PET)-CT scanning with 18F-fluorodeoxy-glucose (18F-FDG) as a surrogate marker of the activity of brown fat, dual-energy X-ray absorptiometry to evaluate body composition, and indirect calorimetry to assess energy expenditure.
Subjects were studied in the morning after an overnight fast. During the study, the research participants reclined under thermoneutral conditions (22° C) for 1 hour and then were exposed to mild cold (16° C, or 60.8° F) for 2 hours. After 1 hour of exposure to cold, the PET tracer 18F-FDG was administered intravenously, and scanning was performed after the second hour of exposure to cold. Three subjects had high levels of brown adipose-tissue activity, and agreed to undergo an additional PET study in thermoneutral conditions to investigate whether brown adipose tissue was activated only after cold exposure.
In addition, a 46-year-old female patient also underwent removal of samples of brown adipose tissue during surgery for multinodular goiter, and the presence and activity of the fat was assessed.
Twenty-three of the 24 male subjects had 18F-FDG activity (the surrogate marker for brown adipose-tissue activity) in the neck, supraclavicular region, chest, and abdomen. On the fused PET-CT images, the activity was located in fat tissue, which was therefore presumed to be brown adipose tissue. The area with the highest activity was the supraclavicular area. All of the lean subjects and 13 of the 14 overweight or obese subjects had evidence of brown adipose-tissue activity in response to cold exposure. However, brown adipose-tissue activity was significantly lower in the overweight or obese subjects (102 ± 93 kBq) than in the lean subjects (428 ± 394 kBq) (P = 0.007). Not only the activity, but also the amount of brown adipose tissue, tended to be lower in the overweight or obese subjects than in the lean subjects. The subject with the highest BMI (38.7 kg/m2) and percentage of body fat (41.8%) had no 18F-FDG uptake in areas of adipose tissue.
On exposure to cold, all subjects had a reduction of skin temperature relative to core temperature and an increase in heat production. The fall in skin temperature was greater in the heavy group than in the ideal body weight group. Body core temperature increased slightly, with lean subjects having a slightly lower increase than obese or overweight subjects. The resting metabolic rate per 24 hours increased significantly in both groups, but was higher in the lean than in the overweight/obese group. The activity of whole-body brown adipose tissue was negatively correlated with BMI and percentage of body fat (r = -0.60; P = 0.001). There was no correlation between brown adipose-tissue activity and age, and in a stepwise regression analysis, BMI but not age was significantly associated with brown adipose-tissue activity.
In the three subjects who agreed to be retested under thermoneutral (normal) conditions, no brown adipose-tissue activity was detected during the normal temperature measurement, although these individuals had demonstrated brown adipose-tissue activity in the cold condition.
Studies of brown adipose tissue (but not white adipose tissue) obtained from the supraclavicular region during surgery in the patient with multinodular goiter revealed the presence of UCP1, suggestive of brown fat activity.
The core temperature under thermoneutral conditions was positively correlated with brown adipose-tissue activity. Further, the change in temperature after cold exposure was related to brown adipose-tissue activity. Finally, the resting metabolic rate correlated with brown adipose-tissue activity during both temperature conditions. These findings suggested to the authors that brown adipose-tissue activity may contribute to the regulation of body temperature by increasing the production of body heat and may be involved in energy metabolism. However, they did not find a significant relation between cold-induced thermogenesis and brown adipose-tissue activity.
Commentary
Like so many scientific articles, this one first came to my attention because of coverage in the lay press and in medical association newsletters. It was actually 1 of 3 studies about brown fat that appeared in same issue of the New England Journal of Medicine. One of these articles reported that brown fat is more common in women than in men, and its amount is inversely correlated with BMI, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.1 The other paper, by Virtanen et al, showed that brown adipose tissue in adult humans can be rapidly activated by exposure to cold temperatures.2 This trio of papers caused a stir in the media. The New York Times noted, "turning down the thermostat to a chilly 61° or so might conceivably help some people lose weight," and provides a readable summary of our knowledge heretofore about brown fat and its activity.3 Brown fat is known to help human infants (who cannot shiver) stay warm in the cold, but had been assumed to atrophy or otherwise vanish in humans as they mature and develop a shivering response. The findings that adults do have brown fat, that it can be activated by cold, and that its presence and activity are reduced in overweight or obese people suggests that the absence of brown fat could be a factor in weight gain.
In the accompanying editorial, Celi notes, "these studies point to a potential 'natural' intervention to stimulate energy expenditure: Turn down the heat and burn calories (and reduce the carbon footprint in the process)."4 Both the lay press and the scientific literature make the leap from the discovery of the association of brown fat with weight to the suggestion that a pill could someday be developed that would somehow increase the amount or activity of brown fat, potentially facilitating weight loss. But I think the New York Times got it right: "But this hoped-for remedy could be a long time in coming, if at all. Its potential is not an excuse to put off dieting and exercise."3
References
1. Cypess AM, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509-1517.
2. Virtanen KA, et al. Functional brown adipose tissue in healthy adults. N Engl J Med 2009;360:1518-1525.
3. "Cool Way to Lose Weight?" New York Times, April 12, 2009, p. 7.
4. Celi FS. Brown adipose tissue when it pays to be inefficient. N Engl J Med 2009;360:1553-1556.
Brown adipose tissue is involved in temperature regulation, and relates to metabolic rate and body mass index. Its activity appears to be reduced in people who are obese.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content