Identification and Importance of Brown Adipose Tissue in Adult Humans

Abstract

BACKGROUND Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. METHODS We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET–CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. RESULTS Substantial depots of brown adipose tissue were identified by PET–CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher 18F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P= 0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P = 0.007). CONCLUSIONS Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of 18F-FDG PET–CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

“…It has been proposed that beige adipocytes can derive from a distinct precursor and display a gene expression pattern different from that of brown adipocytes 9. Recent studies also reported the presence of BAT and the formation of UCP1‐expressing adipocytes within WAT depots in adult humans 10, 11. In humans, UCP1‐positive adipocytes exhibiting both brown12, 13, 14 and beige13, 14, 15, 16 molecular signatures have been described.…”

Biological aging alters circadian mechanisms in murine adipose tissue depots

“…Visceral WAT accumulates with advancing age in men and women (Weisberg et al 2003;Ortega et al 2008;Gavi et al 2007), and inflammatory processes within visceral WAT place the elderly at increased risk for metabolic syndrome, diabetes, and cardiovascular disease (Trayhurn and Beattie 2001;Trayhurn 2005;Cartwright et al 2007;Huffman and Barzilai 2009). Recent evidence indicates that thermogenic brown fat decreases with age and this change contributes to obesity (Nedergaard et al 2007;Cypess et al 2009;van Marken Lichtenbelt et al 2009;Virtanen et al 2009). Furthermore, biological aging is associated with increased bone marrow adipogenesis, an etiologic factor underlying osteopenia and osteoporosis (Meunier et al 1971;Gimble et al 2006).…”

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

“…1 Obesity is defined by the expansion of white adipose tissue (WAT), but recent evidence suggests that the adult human body also contains functionally distinct, brown adipose tissue. [2][3][4][5][6][7][8] In contrast to WAT, which has a primary role in energy storage, brown adipose tissue specializes in energy dissipation as heat (Cannon and Nedergaard 9 ). This thermogenic property of brown fat results from its high content of mitochondria, cell organelles where energy dissipation occurs.…”