title: Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women.
abstract: BACKGROUND
  Subcutaneous adipose tissue is an interesting source of autologous stem cells with a fundamental role in the pathophysiology of obesity, metabolic syndromes and insulin resistance. We hypothesize that obesity could alter the stromal-vascular fraction (SVF) and adipose stem cell (ASCs) functions, which could compromise its regenerative behavior. Furthermore, we aimed to evaluate whether ASCs derived from post bariatric surgery ex-obese women maintain their functions in a similar fashion as do those from individuals who have never been obese.
  
  
  METHODS
  The SVF of subcutaneous adipose tissue from control (n = 6, body mass index - BMI - 27.5 ± 0.5 kg/m(2)), obese (n = 12, BMI 46.2 ± 5.1 kg/m(2)) and post bariatric surgery ex-obese (n = 7, initial BMI 47.8 ± 1.3 kg/m(2); final BMI 28.1 ± 1.1 kg/m(2)) women were isolated and evaluated by flow cytometry. ASCs were tested for lipid accumulation by perilipin, adipose differentiation-related protein (ADRP) and Oil Red O staining after adipogenic stimulus. The cytokines secreted by the ASCs and after lipid accumulation induction were also evaluated.
  
  
  RESULTS
  The subcutaneous adipose tissue of obese and post bariatric surgery ex-obese women was enriched in pericytes (p = 0.0345). The number of supra-adventitial cells was not altered in the obese patients, but it was highly enriched in the post bariatric surgery ex-obese women (p = 0.0099). The ASCs of the post bariatric surgery ex-obese patients secreted more MCP-1 (monocyte chemoattractant protein-1; p = 0.0078). After lipid accumulation induction, the ASCs of the patients in all groups secreted less IL-6 than the ASCs with no adipogenic stimulus (p < 0.0001). Obese ASCs with lipid accumulation secreted the highest amount of IL-6 (p < 0.001) whereas the ASCs from the controls secreted the highest amount of adiponectin (p < 0.0001). The ASCs from the post bariatric surgery ex-obese patients showed the highest levels of lipid accumulation whereas those from the obese women had the lowest levels (p < 0.0001).
  
  
  CONCLUSIONS
  SVF content and ASC behavior are altered in the subcutaneous adipose tissue of morbid obese women; these changes are not completely restored after bariatric surgery-induced weight loss. The cellular alterations described in this study could affect the regenerative effects of adipose stem cells. Further investigations are required to avoid jeopardizing the development of autologous stem cell-based therapies.
authors.affiliation: Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. karinaribeiro@biof.ufrj.br.|Núcleo Multidisciplinar de Pesquisa UFRJ - Xerém em Biologia (Numpex-Bio), Universidade Federal do Rio de Janeiro, Polo Xerém, Duque de Caxias, RJ 25245-390, Brazil. karinaribeiro@biof.ufrj.br.|Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil. karinaribeiro@biof.ufrj.br.
authors.forename: Karina R
authors.initials: KR
authors.lastname: Silva
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ 21.040-900, Brazil. sally.liechocki@ioc.fiocruz.br.
authors.forename: Sally
authors.initials: S
authors.lastname: Liechocki
authors.affiliation: Departamento de Nutrologia do Hospital Universitário Clementino Fraga Filho, Universidade Fereal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. endoregis@hucff.ufrj.br.
authors.forename: João R
authors.initials: JR
authors.lastname: Carneiro
authors.affiliation: Serviço de Cirurgia Plástica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. cscesar@hucff.ufrj.br.
authors.forename: Cesar
authors.initials: C
authors.lastname: Claudio-da-Silva
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ 21.040-900, Brazil. clarissa@ioc.fiocruz.br.
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Maya-Monteiro
authors.affiliation: Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. radovan@histo.ufrj.br.|Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil. radovan@histo.ufrj.br.
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.affiliation: Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. leandrabaptista@xerem.ufrj.br.|Núcleo Multidisciplinar de Pesquisa UFRJ - Xerém em Biologia (Numpex-Bio), Universidade Federal do Rio de Janeiro, Polo Xerém, Duque de Caxias, RJ 25245-390, Brazil. leandrabaptista@xerem.ufrj.br.|Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil. leandrabaptista@xerem.ufrj.br.
authors.forename: Leandra S
authors.initials: LS
authors.lastname: Baptista
mesh_terms: D050156:Adipogenesis; D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D063194:Adventitia / Q000166:cytology / Q000378:metabolism; D050110:Bariatric Surgery; D015992:Body Mass Index; D002352:Carrier Proteins / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000166:cytology*
chemical_list: D052242:Adiponectin; C111835:CCL2 protein, human; D002352:Carrier Proteins; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins