title: The FAT expandability (FATe) Project: Biomarkers to determine the limit of expansion and the complications of obesity.
abstract: BACKGROUND
  Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells.
  
  
  METHODS
  FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance.
  
  
  CONCLUSIONS
  The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain. etorresp.iacs@aragon.es.|Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain. etorresp.iacs@aragon.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Torres-Perez
authors.affiliation: Unidad de Cirugía, Hospital Royo Villanova, Zaragoza, Spain. mvalsaba@hotmail.com.
authors.forename: Monica
authors.initials: M
authors.lastname: Valero
authors.affiliation: Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, Spain. bea_garcia_rodriguez@hotmail.com.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garcia-Rodriguez
authors.affiliation: Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, Spain. yolgonira@gmail.com.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Gonzalez-Irazabal
authors.affiliation: Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, Spain. mpcalmarza@salud.aragon.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Calmarza
authors.affiliation: Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, Spain. mlcalvo@salud.aragon.es.
authors.forename: Luisa
authors.initials: L
authors.lastname: Calvo-Ruata
authors.affiliation: Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, Spain. cortegama@salud.aragon.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ortega
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain. jmarbones.iacs@aragon.es.|Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain. jmarbones.iacs@aragon.es.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Garcia-Sobreviela
authors.affiliation: Servicio de Endocrinología y Nutrición, Hospital Universitario Miguel Servet, Zaragoza, Spain. sanzparisalejandro@gmail.com.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanz-Paris
authors.affiliation: Servicio de Radiodiagnóstico, Hospital Universitario Miguel Servet, Zaragoza, Spain. jmartigasm@gmail.com.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Artigas
authors.affiliation: Unidad de Cirugía, Hospital Royo Villanova, Zaragoza, Spain. jlagos@comz.org.
authors.forename: Javier
authors.initials: J
authors.lastname: Lagos
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain. jmarbones.iacs@aragon.es.|Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain. jmarbones.iacs@aragon.es.|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: D050154:Adiposity / Q000208:ethnology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018450:Disease Progression; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006801:Humans; D055432:Metabolomics / Q000379:methods; D009765:Obesity / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D050151:Subcutaneous Fat / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers