Role of PRDM16 in the activation of brown fat programming. Relevance to the development of obesity
Sara Becerril1,2, Javier Gómez-Ambrosi1,2, Marina Martín3, Rafael Moncada4, Pilar Sesma3, María A. Burrell2,3 and Gema Frühbeck1,2,5
1Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain, 2CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain, 3Department of Histology and Pathology, University of Navarra, Pamplona, Spain, 4Department of Anesthesiology, Clínica Universidad de Navarra, Pamplona, Spain and 5Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
Offprint requests to: Sara Becerril, PhD, Metabolic Research Laboratory, Clinica Universidad de Navarra, Avda. Pío XII, 36, 31008 Pamplona, Spain. e-mail: sbecman@unav.es
Summary. From a histological and functional point of view, two types of adipose tissue can be identified. As opposed to the mainly unilocular white adipocytes, brown adipocytes possess plenty of small multilocular lipid droplets and dissipate energy as heat. Moreover, two distinct types of brown adipose cells exist. In vivo fate mapping experiments of brown adipose tissue (BAT) precursors suggest that classical brown adipocytes and skeletal myoblasts originate from a common mesenchymal, myogenic factor 5 (Myf5)-positive precursor cell. In addition to the classical brown adipocytes, thermogenic brown-like adipocytes (brite/beige cells) may appear within white adipose tissue (WAT) depots, sharing many of the morphological and functional features of brown adipocytes, but arising from a Myf5-negative lineage. In humans, the conversion of white fat cells into brite adipocytes could be a strategy to increase energy expenditure. The zinc finger transcription factor Prdm16 controls the bidirectional fate decision between brown adipocytes and myoblasts. Prdm16 determines the brown fat-like programme and thermogenesis in both brown and white adipose tissues. Moreover, the expression of this transcriptional regulator is strongly correlated with beige cell-selective genes. From a therapeutical point of view, the potential of inducing BAT or the transdifferentiation of WAT into beige cells by enhancing Prdm16 expression, as well as the identification of mechanisms of Prdm16 function and regulation represent potentially exciting new approaches for treatment or prevention of obesity and related diseases. Histol Histopathol 28, 1411-1425 (2013)
Key words: Brown adipose tissue, PRDM16, Transdifferentiation, Thermogenesis, Obesity
DOI: 10.14670/HH-28.1411