To lose weight, would you rather diet, exercise or subject yourself to cool temperatures? The last choice is not such an odd one, as adult humans have brown fat tissue that burns calories in response to cold.
Fat is mainly stored in two types of adipose tissue: white and brown. White adipose tissue stores calories as large lipid droplets within individual cells. By contrast, brown adipose tissue (BAT) stores little fat, instead burning it to produce heat and regulate body temperature. Small mammals and newborn humans have copious amounts of BAT around their shoulder blades, which helps them to survive cold temperatures. Adult humans, however, were largely thought to lack BAT, with only one investigation1 describing adipose tissue that seemed to function as BAT. Three independent studies2,3,4, just published in The New England Journal of Medicine, follow up this observation, and conclusively identify BAT in adult humans.
BAT's ability to burn rather than store calories depends on each brown fat cell having many mitochondria — organelles that function as cells' power plants. Mitochondria are also abundant in the skeletal and heart muscles, and in the brain, where they convert metabolized sugars (glucose) and fats into the highly energized ATP molecule to fuel organismal activities. The mitochondria of brown fat cells are unique in that they contain UCP1, a protein that uncouples metabolism from ATP production in order to produce heat5.
To detect BAT in adult humans, all three studies2,3,4 used 18FDG-based positron emission tomography/computerized tomography (PET/CT). This medical imaging technique measures the absorption of consumed 18F-fluorodeoxyglucose (18FDG) — a harmless radioactive form of glucose — into various tissues, providing information about the metabolic activity of each tissue. For definitive identification of BAT, the authors also performed histological and biochemical analysis of UCP1 in tissue biopsy samples.
In small mammals, exposure to cold stimulates the sympathetic nervous system to release the hormone adrenaline, which triggers brown fat cells to consume more fat and glucose for heat production. Virtanen et al.2 scanned healthy volunteers on two separate days: on one day at normal room temperature; and on the other at 17–19 °C while volunteers immersed one foot in cold (7–9 °C) water for 5 minutes, every other 5 minutes. In all individuals, exposure to cold led to a 15-fold increase in 18FDG uptake into the adipose tissue of the collarbone (supraclavicular) region. Tissue biopsy of precisely this region in three of the volunteers, based on morphology and UCP1 expression, revealed the presence of BAT. The authors detected 63 grams of supraclavicular BAT in one of the individuals — a mass they estimate could burn the equivalent amount of energy during a year as is stored in about 4 kilograms of white fat tissue.
Van Marken Lichtenbelt et al.3 examined the presence, distribution and activity of BAT in 10 lean and 14 overweight/obese men in relation to body composition — percentage fat and lean-muscle mass — and energy metabolism. They report BAT activity in 23 of 24 individuals when measured at 16 °C, but not at 22 °C. The one individual with no BAT activity also had the highest percentage (42%) of body fat. In fact, BAT activity within the group showed a significant negative correlation with percentage body fat and correlated positively with resting metabolic rate.
Excess storage of fat disrupts metabolic balance, leading to obesity-related disorders, such as diabetes and cardiovascular disease, which are collectively known as metabolic syndrome6. When fat accumulates in the intra-abdominal regions around internal organs — as it does mostly in men — the risk of developing metabolic syndrome is highest; women, by contrast, are at a lower risk, because they often store fat under the skin, around the thighs and buttocks7 (Fig. 1). Cypess and colleagues4 analysed 3,640 previously recorded scans of 1,972 patients (both men and women) who had undergone 18FDG-PET/CT diagnostic screening for various medical reasons. The authors find scans corresponding to BAT activity in 7.5% of women and 3.1% of men. Moreover, women had a greater BAT mass, which absorbed more 18FDG.
Larger amounts of active BAT also showed a positive correlation with younger age and lower outdoor temperature on the day each patient was scanned4. The authors detected an inverse relationship between active BAT and both smoking and patients' use of beta-blocker drugs for the treatment of high blood pressure and cardiovascular disease.
It is likely that the percentage of positive BAT scans Cypess et al. observed is lower compared with the other two reports2,3 because the authors4 relied on scans that were performed only at room temperatures. These studies, however, reach several similar conclusions: irrespective of age and gender, adult humans contain metabolically active BAT in their neck and upper chest regions; cold temperatures can activate BAT in adult humans, apparently more often in women than in men; and the presence of BAT correlates inversely with body fat, especially in older people.
Having reached pandemic levels worldwide, obesity and its related diseases have drastically increased health-care costs. With a role in adult-human metabolism, could BAT be exploited as a therapy for obesity?
For individuals with metabolically active BAT, one way to lose weight might simply be exposure to cold. As for others, years of investigation into the formation and function of BAT in mice has provided a wealth of knowledge that could aid the development of anti-obesity therapies targeting BAT in adult humans. For instance, weight loss might be achieved through drugs that mimic the cold by activating the sympathetic nervous system. Enhancing the formation of BAT, rather than white adipose tissue, might be another useful strategy. Such an enterprise has recently come closer to realization with the discovery8,9,10 of the stem-cell origins of the two adipose tissues. Moreover, the BMP7 protein has been identified11 as the factor that selectively controls the growth and development of brown fat cells, and so drugs that mimic its action might also be effective anti-obesity agents.
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About this article
Identification of New Potent Human Uncoupling Protein 1 (UCP1) Agonists Using Virtual Screening and in vitro Approaches
Molecular Informatics (2019)
Journal of Biological Chemistry (2019)
Contrast Media & Molecular Imaging (2018)
Cell Reports (2018)
Molecular Imaging and Biology (2018)