Mini-review UCP1 protein: The molecular hub of adipose organ plasticity Saverio Cinti Dpt. Experimental and Clinical Medicine, University of Ancona (Politecnica delle Marche), Via Tronto 10a, 60020, Ancona, Italy article info Article history: Received 29 July 2016 Accepted 8 September 2016 Available online xxx Keywords: UCP1 White adipocytes Brown adipocytes Pink adipocytes CLS abstract In all mammals, adipocytes are cells with abundant cytoplasmic lipids forming the parenchyma of the adipose organ. White adipocytes store highly energetic molecules to release them, in the form of free fatty acids to survive between meals. Brown adipocytes trough their unique mitochondrial UCP1 protein burn glucose and lipids to perform thermogenesis in order to survive in cold environments. A third type of adipocytes appears in the subcutaneous depot of the adipose organ of female mice during pregnancy and lactation: the pink adipocytes. The pink adipocytes are mammary gland alveolar epithelial cells with the essential role of producing and secreting milk for pup feeding. Our data suggest that they derive from the transdifferentiation of white adipocytes. Different metabolic and environmental challenges highlight the extraordinary plasticity of the mammalian adipose organ. Cold exposure leads to an increase of the “brown” component of the adipose organ (browning) to warrant thermal homeostasis. Under positive energy balance, the “white” component enlarges (whitening) to allow storage of the excess of nutrients. Finally, during pregnancy the “pink” component develops (pinking) in the subcutaneous depots to satisfy pup nutritional needs. The plasticity of the adipose organ appears to occur not only through proliferation and differentiation of stem cells but, distinctively, via a direct transformation of mature adipocytes that under proper stimuli, by reprogramming their genome, change phenotype and function. Obese white adipocytes die for pyroptosis causing a macrophage fat infiltration with metabolic con- sequences. Browning of obese fat could offer an appropriate strategy to combat the epidemic metabolic syndrome. © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved. 1. White and brown adipocytes In adult mammals two adipose tissues are present: white (WAT) and brown (BAT) adipose tissues. WAT and BAT are organized to form an organ with two compartments: subcutaneous and visceral (Fig. 1). Both compartments contain WAT and BAT [1,2]. Historically they are denominated adipose tissues because their respective parenchymal cells are able to store abundant cytoplasmic lipids, but several anatomical characteristics account for their different and almost opposite physiologic role: white adipocytes are spherical large cells with a unilocular cytoplasmic lipid droplet that store energy to allow survival of the organism between meals (Fig. 2). This was of vital importance when it was necessary to catch for food and even risk the life for it (i.e. since prehistory to about one hundred years ago) giving the possibility of two-three weeks of fasting before a new meal. Brown adipocytes are polygonal cells (Fig. 2) with multilocular cytoplasmic lipid droplets and numerous characteristic large mitochondria packed with laminar cristae. When physiologically stimulated by cold exposure, brown adipocytes burn lipids to produce heat. Cold is the main but not the only one stimulus for BAT activa- tion: stress, cachexia, natural compounds and drugs can also acti- vate BAT [3]. The multilocular lipid organization greatly increases the lipid-jaloplasm interface allowing a quick release of large amounts of fatty acids ready for the mitochondria beta-oxidation. The main molecular mechanism for brown adipocyte thermogen- esis is due to the protein UCP1 [4e6] that is uniquely present in this cell type [7]. Food intake also activates brown adipocytes [8] and energy dissipated by BAT is important to prevent obesity [9,10], type 2 diabetes (T2D) [11e13] and atherosclerosis [14,15], thus BAT activation is now a day regarded as one of the possible strategy to combat the epidemic metabolic syndrome [16e19]. 2. Adipose tissues plasticity Loncar first described the phenomenon of convertibility of WAT E-mail address: cinti@univpm.it. Contents lists available at ScienceDirect Biochimie journal homepage: www.elsevier.com/locate/biochi http://dx.doi.org/10.1016/j.biochi.2016.09.008 0300-9084/© 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved. Biochimie xxx (2016) 1e6 Please cite this article in press as: S. Cinti, UCP1 protein: The molecular hub of adipose organ plasticity, Biochimie (2016), http://dx.doi.org/ 10.1016/j.biochi.2016.09.008