LAUSR

The last decade has witnessed an enormous interest of scientists and clinicians in the understanding of the biological activity of brown adipose tissue (BAT) and its role in health and disease. The importance of BAT as a relevant site of adaptive energy expenditure and protective properties against obesity and other metabolic alterations were growingly recognized in experimental animals after the seminal studies by Rothwell and Stock [22] and others in the late 1970s of the last century. However, the “re-discovery” of active BAT in adult humans in the last decade [11] has stimulated an unprecedented interest in BAT research. BAT is a thermogenic tissue which main function is energy dissipation. Brown adipocyte thermogenesis is driven through uncoupling protein 1 (UCP1)-dependent and possibly also through UCP1-independent mechanisms (i.e., creatinedependent substrate cycling, calcium-dependent ATP hydrolysis, lipid cycling) [8, 14]. BAT activity is inversely related to body fatness, and experimental suppression or activation of BAT leads to increased or decreased adiposity, respectively, indicating that BAT activation is protective against obesity. BAT activation is also involved in other metabolic roles, including control of glucose homeostasis and insulin sensitivity, as well as triglyceride clearance [1, 6, 7, 13]. BAT has also emerged as an active secretory organ that produces brown adipokines or “batokines,” which may play an autocrine/paracrine role regulating the thermogenic function of brown adipocytes or other BAT cells (immune cells) or act as endocrine signals controlling the function of many other tissues including the liver, muscle, and white adipose tissue (WAT), among others [2, 4, 24] . In addition to the so-called “classical” brown adipocytes, beige or brite (from “brown-in-white”) adipocytes have been identified as a distinct type of adipose cells in rodents and humans sharing thermogenic properties with brown adipocytes [26]. The beige/brite adipocytes appear in WAT depots in a highly inducible manner through the process called adipose tissue “browning.” The molecular characterization of BAT in adult humans has suggested that it may be composed of both classical brown adipocytes and beige/brite adipocytes [17, 23]. Although the relevant contribution of beige fat in the regulation of energy balance is controversial, a growing body of evidence suggests that stimulating the recruitment and activity of classical brown and beige adipocytes constitutes a promising strategy against obesity and its deleterious associated-disorders [18]. The abundance of brown/beige fat is reduced with obesity and aging. One of the current challenges is to unravel the mechanisms promoting the reduction of BAT/beige activity during aging, especially in humans, and to look for effective strategies to prevent BAT loss or to reactivate existing BAT depots [10]. The classically recognized mechanisms of control of BAT and beige adipose tissue rely on the sympathetic nervous María J. Moreno-Aliaga and Francesc Villarroya contributed equally to this work.