title: Sirtuins 1-7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia.
abstract: The sirtuin family comprises seven NAD+-dependent deacetylases which control the overall health of organisms through the regulation of pleiotropic metabolic pathways. Sirtuins are important modulators of adipose tissue metabolism and their expression is higher in lean than obese subjects. At present, the role of sirtuins in adipose-derived stem cells has not been investigated yet. Therefore, in this study, we evaluated the expression of the complete panel of sirtuins in adipose-derived stem cells isolated from both subcutaneous and visceral fat of non-obese and obese subjects. We aimed at investigating the influence of obesity on sirtuins' levels, their role in obesity-associated inflammation, and the relationship with the peroxisome proliferator-activated receptor delta, which also plays functions in adipose tissue metabolism. The mRNA levels in the four types of adipose-derived stem cells were evaluated by quantitative polymerase chain reaction, in untreated cells and also after 8 h of hypoxia exposure. Correlations among sirtuins' expression and clinical and molecular parameters were also analyzed. We found that sirtuin1-6 exhibited significant higher mRNA expression in visceral adipose-derived stem cells compared to subcutaneous adipose-derived stem cells of non-obese subjects. Sirtuin1-6 levels were markedly reduced in visceral adipose-derived stem cells of obese patients. Sirtuins' expression in visceral adipose-derived stem cells correlated negatively with body mass index and C-reactive protein and positively with peroxisome proliferator-activated receptor delta. Finally, only in the visceral adipose-derived stem cells of obese patients hypoxia-induced mRNA expression of all of the sirtuins. Our results highlight that sirtuins' levels in adipose-derived stem cells are consistent with protective effects against visceral obesity and inflammation, and suggest a transcriptional mechanism through which acute hypoxia up-regulates sirtuins in the visceral adipose-derived stem cells of obese patients.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mariani
authors.affiliation: Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Di Rocco
authors.affiliation: Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Toietta
authors.affiliation: Consorzio MEBIC, San Raffaele University, Laboratory of Molecular and Cellular Pathology, Rome, Italy.
authors.forename: Matteo A
authors.initials: MA
authors.lastname: Russo
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Petrangeli
authors.affiliation: Institute of Molecular Biology and Pathology, CNR, Rome, Italy. luisa.salvatori@uniroma1.it.
authors.forename: Luisa
authors.identifier: http://orcid.org/0000-0003-2286-9869
authors.initials: L
authors.lastname: Salvatori
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D054337:Cell Dedifferentiation; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050177:Overweight / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D050507:Subcutaneous Fat, Abdominal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D007527:Isoenzymes; D047494:PPAR delta; D012333:RNA, Messenger; D002097:C-Reactive Protein; D037761:Sirtuins
keywords: Adipose-derived stem cells; Hypoxia; Inflammation; Obesity; Peroxisome proliferator-activated receptor delta; Sirtuins