title: White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma.
abstract: In all mammals, white adipose tissue (WAT) and brown adipose tissue (BAT) are found together in several fat depots, forming a multi-depot organ. Adrenergic stimulation induces an increase in BAT usually referred to as "browning". This phenomenon is important because of its potential use in curbing obesity and related disorders; thus, understanding its cellular mechanisms in humans may be useful for the development of new therapeutic strategies. Data in rodents have supported the direct transformation of white into brown adipocytes. Biopsies of pure white omental fat were collected from 12 patients affected by the catecholamine-secreting tumor pheochromocytoma (pheo-patients) and compared with biopsies from controls. Half of the omental fat samples from pheo-patients contained uncoupling protein 1 (UCP1)-immunoreactive-(ir) multilocular cells that were often arranged in a BAT-like pattern endowed with noradrenergic fibers and dense capillary network. Many UCP1-ir adipocytes showed the characteristic morphology of paucilocular cells, which we have been described as cytological marker of transdifferentiation. Electron microscopy showed increased mitochondrial density in multi- and paucilocular cells and disclosed the presence of perivascular brown adipocyte precursors. Brown fat genes, such as UCP1, PR domain containing 16 (PRDM16) and β3-adrenoreceptor, were highly expressed in the omentum of pheo-patients and in those cases without visible morphologic re-arrangement. Of note, the brown determinant PRDM16 was detected by immunohistochemistry only in nuclei of multi- and paucilocular adipocytes. Quantitative electron microscopy and immunohistochemistry for Ki67 suggest an unlikely contribution of proliferative events to the phenomenon. The data support the idea that, in adult humans, white adipocytes of pure white fat that are subjected to adrenergic stimulation are able to undergo a process of direct transformation into brown adipocytes. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.
authors: Department of Experimental and Clinical Medicine, Center for the Study of Obesity-United Hospitals University of Ancona, 60126 Ancona, Italy.
authors: Andrea
authors: A
authors: Frontini
authors: Alessandra
authors: A
authors: Vitali
authors: Jessica
authors: J
authors: Perugini
authors: Incoronata
authors: I
authors: Murano
authors: Chiara
authors: C
authors: Romiti
authors: Daniel
authors: D
authors: Ricquier
authors: Mario
authors: M
authors: Guerrieri
authors: Saverio
authors: S
authors: Cinti
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology* / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D054338:Cell Transdifferentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009852:Omentum / Q000166:cytology* / Q000378:metabolism; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D004268:DNA-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C416371:PRDM16 protein, human; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D014157:Transcription Factors; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1