title: Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.
abstract: Impaired adipogenesis renders an adipose tissue unable to expand, leading to lipotoxicity and conditions such as diabetes and cardiovascular disease. While factors important for adipogenesis have been studied extensively, those that set the limits of adipose tissue expansion remain undetermined. Feeding a Western-type diet to apolipoprotein E2 knock-in mice, a model of metabolic syndrome, produced 3 groups of equally obese mice: mice with normal glucose tolerance, hyperinsulinemic yet glucose-tolerant mice, and prediabetic mice with impaired glucose tolerance and reduced circulating insulin. Using proteomics, we compared subcutaneous adipose tissues from mice in these groups and found that the expression of PTRF (polymerase I and transcript release factor) associated selectively with their glucose tolerance status. Lentiviral and pharmacologically overexpressed PTRF, whose function is critical for caveola formation, compromised adipocyte differentiation of cultured 3T3-L1cells. In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. Furthermore, a negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. PTRF is associated with limited adipose tissue expansion underpinning the key role of caveolae in adipocyte regulation. Furthermore, PTRF may be a suitable adipocyte marker for predicting pathological obesity and inform clinical management.
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Hospital Universitario Miguel Servet, Zaragoza, Spain;
authors.forename: Sergio
authors.initials: S
authors.lastname: Perez-Diaz
authors.affiliation: Department of Pathology and Laboratory Medicine and.
authors.forename: Lance A
authors.initials: LA
authors.lastname: Johnson
authors.affiliation: University of North Carolina Systems-Proteomics Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;
authors.forename: Robert M
authors.initials: RM
authors.lastname: DeKroon
authors.affiliation: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona (IdlBGi) Hospital Dr. Josep Trueta, Girona, Spain; and Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.affiliation: University of North Carolina Systems-Proteomics Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;
authors.forename: Oscar
authors.initials: O
authors.lastname: Alzate
authors.affiliation: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona (IdlBGi) Hospital Dr. Josep Trueta, Girona, Spain; and Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Fernandez-Real
authors.affiliation: Department of Pathology and Laboratory Medicine and.
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Hospital Universitario Miguel Servet, Zaragoza, Spain; Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain jmarbones.iacs@aragon.es.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Arbones-Mainar
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000473:pathology*; D050156:Adipogenesis / Q000502:physiology*; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001011:Aorta / Q000473:pathology; D053329:Apolipoprotein E2 / Q000235:genetics; D021941:Caveolae / Q000502:physiology*; D016922:Cellular Senescence; D004032:Diet / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D055879:Gene Knock-In Techniques; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology* / Q000473:pathology; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000209:etiology* / Q000473:pathology; D007333:Insulin Resistance; D008066:Lipolysis; D008099:Liver / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000145:classification / Q000209:etiology* / Q000473:pathology; D011236:Prediabetic State / Q000097:blood / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000473:pathology; D059506:Telomere Shortening; D014280:Triglycerides / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D053329:Apolipoprotein E2; C497835:CAVIN1 protein, human; C112745:Cavin1 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014280:Triglycerides
keywords: glucose intolerance; senescence; telomeres