Brown Adipose Tissue in Adult Humans: A Metabolic Renaissance

Abstract

Brown adipose tissue (BAT) plays a key role in energy homeostasis and thermogenesis in animals, conferring protection against diet-induced obesity and hypothermia through the action of uncoupling protein 1 (UCP1). Recent metabolic imaging studies using positron emission tomography computerized tomography (PET-CT) scanning have serendipitously revealed significant depots of BAT in the cervical-supraclavicular regions, demonstrating persistence of BAT beyond infancy. Subsequent cold-stimulated PET-CT studies and direct histological examination of adipose tissues have demonstrated that BAT is highly prevalent in adult humans. BAT activity correlates positively with increment of energy expenditure during cold exposure and negatively with age, body mass index, and fasting glycemia, suggesting regulatory links between BAT, cold-induced thermogenesis, and energy metabolism. Human BAT tissue biopsies express UCP1 and harbor inducible precursors that differentiate into UCP1-expressing adipocytes in vitro. These recent discoveries represent a metabolic renaissance for human adipose biology, overturning previous belief that BAT had no relevance in adult humans. They also have implications for the understanding of the pathogenesis and treatment of obesity and its metabolic sequelae.

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology

“…It has been also found in neonates of large mammalian species and more recently, in adults (Lee et al, 2013). As observed in human, BAT depots in sheep are mainly found in the supraclavicular/ neck region and in the pericardial and perirenal regions (Symonds et al, 2015).…”

Brown adipose tissue: what have we learned since its recent identification in human adults

“…PET-FDG is a functional exam characterized by its ability to detect metabolically active areas that uptake FDG, a glucose radioisotope (23,30,31). It began being used in the 90s, mainly in oncology, to detect tumors and metastases, which generally have a high metabolic rate and therefore high glucose uptake.…”

“…Although the total mass of brown adipose tissue in mammals is small, past research has already demonstrated that its activation could quadruple the energy expenditure (EE) of an animal, as an increase in tissue perfusion occurs (15,(21)(22)(23). Not only the fat stored in its lipid droplets are used to generate heat, but also free fatty acids and glucose from systemic circulation, exponentially increasing its thermogenic capacity (15).…”

“…This greater area increases heat loss to the environment and costs more energy, used by brown adipose tissue, to maintain thermoregulation. Human newborns possess a high area/volume ratio, and it has long been documented that brown adipose tissue is present in our early life (2,23,(26)(27)(28). However, with the progressive reduction of surface area in relation to internal volume, the energy cost of thermoregulation is decreased and it was believed that brown adipose tissue suffered progressive involution until its total disappearance during early childhood (23).…”

“…Human newborns possess a high area/volume ratio, and it has long been documented that brown adipose tissue is present in our early life (2,23,(26)(27)(28). However, with the progressive reduction of surface area in relation to internal volume, the energy cost of thermoregulation is decreased and it was believed that brown adipose tissue suffered progressive involution until its total disappearance during early childhood (23). The invention and then popularization of PET-FDG changed this view however, as it was hypothesized that at least a fraction of humans still present brown adipose tissue in adult life, as the detection, in a fraction of exams, of areas of metabolic activity raised the possibility of there being unnoticed thermogenic fat (15,23,29).…”