title: Circulating pigment epithelium-derived factor levels are associated with insulin resistance and decrease after weight loss.
abstract: OBJECTIVE
  We aimed to study circulating pigment epithelium-derived factor (PEDF) in vivo in association with insulin resistance and in vitro in human adipocytes.
  
  
  METHODS
  Circulating PEDF (ELISA) and metabolic profile were assessed in 125 Caucasian men. PEDF levels were also assessed in an independent cohort of subjects (n = 33) to study the effects of changing insulin action. PEDF gene expression and secretion were measured during differentiation of human preadipocytes.
  
  
  RESULTS
  In all subjects, PEDF was positively associated with body mass index (r = 0.326; P < 0.0001), waist-to-hip ratio (r = 0.380; P < 0.0001), HbA(1c), and fasting triglycerides and negatively with insulin sensitivity (r = -0.320; P < 0.0001). PEDF levels were significantly increased in subjects with altered glucose tolerance and type 2 diabetes. Of the inflammatory markers measured, PEDF levels were positively associated with serum soluble TNF-α receptor 1 and IL-10 in obese subjects. Interestingly, weight loss led to significantly decreased PEDF concentration from 34.8 ± 19.3 to 22.5 ± 14.2 μg/ml (P < 0.0001). Multiple linear regression analyses revealed that insulin sensitivity contributed independently to explain 14% of the variance in PEDF levels after controlling for the effects of body mass index, age, and log fasting triglycerides. Differences in PEDF observed after weight loss were related to changes in obesity, insulin resistance, and blood pressure measures. PEDF gene expression and secretion increased during differentiation of human preadipocytes.
  
  
  CONCLUSIONS
  Circulating PEDF is associated with insulin sensitivity. The findings show, for the first time in humans, that PEDF concentrations decrease significantly after weight loss in association with blood pressure. PEDF seems to be involved in human adipocyte biology.
authors.affiliation: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Instituto de Salud Carlos III, Girona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Sabater
authors.forename: Jose M
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Ortega
authors.forename: Gerard
authors.initials: G
authors.lastname: Pardo
authors.forename: Javier
authors.initials: J
authors.lastname: Salvador
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D031204:Caloric Restriction; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D004038:Diet, Reducing; D005136:Eye Proteins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology; D015843:Serpins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor