title: Effect of rosiglitazone on capillary density and angiogenesis in adipose tissue of normoglycaemic humans in a randomised controlled trial.
abstract: OBJECTIVE
  Recent reports of decreased capillary density in the adipose tissue of obese individuals suggest that an imbalance of angiogenesis and adipogenesis may, in part, underlie insulin resistance. This study aimed to determine whether the insulin-sensitising peroxisome proliferator-activated receptor γ (PPARγ) activator rosiglitazone affects adipose tissue vascularisation in normal humans.
  
  
  METHODS
  A randomised, parallel-group, investigator-blinded placebo-controlled trial was conducted with normoglycaemic volunteers with BMI 27-43, recruited from the community at the University of Massachusetts Medical School, Worcester, MA, USA. Peri-umbilical adipose tissue biopsies were obtained before and after treatment for 6 weeks with rosiglitazone (8 mg once daily) or placebo, which were randomly allocated from a sequentially numbered list. The primary outcomes were adipocyte size and capillary density measured by immunohistochemistry, and angiogenic potential assessed by capillary sprout formation in Matrigel. Secondary outcomes were serum adiponectin, glycaemic, lipid and liver function variables.
  
  
  RESULTS
  A total of 35 individuals fulfilling the inclusion criteria were randomised, and complete before-vs-after analyses were achieved in 30 participants (13 and 17, placebo and rosiglitazone, respectively). Significant differences, assessed by paired two-tailed Student t tests, were seen in response to rosiglitazone for adipocyte size (3,458 ± 202 vs 2,693 ± 223 μm(2), p = 0.0049), capillary density (5.6 ± 0.5 vs 7.5 ± 0.5 lumens/field, p = 0.0098), serum adiponectin (14.3 ± 1.5 vs 28.6 ± 3.0 ng/ml, p < 0.0001) and alkaline phosphatase (1.04 ± 0.07 vs 0.87 ± 0.05 μkat/l, p = 0.001). A difference in angiogenic potential before and after treatment between the placebo and rosiglitazone groups was also seen (-23.88 ± 14 vs 13.42 ± 13, p = 0.029, two-tailed Mann-Whitney test).
  
  
  CONCLUSIONS
  Significant effects on adipose tissue vascular architecture occur after a short period of treatment with rosiglitazone in individuals with normal glucose tolerance. Improved adipose tissue vascularisation may, in part, mediate the therapeutic actions of this class of drugs.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01150981
  
  
  BACKGROUND
  The study was funded by National Institutes of Health grant DK089101 to S. Corvera, and by pilot funding from the University of Massachusetts (UMASS) Center for Clinical Translational Sciences (M. Thompson, S. Malkani and S. Corvera). Morphology core services were supported by UMASS Diabetes Endocrine Research Center (DERC) grant DK32520.
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01615, USA.
authors: O
authors: O
authors: Gealekman
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
authors: N
authors: N
authors: Guseva
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01615, USA.
authors: K
authors: K
authors: Gurav
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01615, USA.
authors: A
authors: A
authors: Gusev
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
authors: C
authors: C
authors: Hartigan
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
authors: M
authors: M
authors: Thompson
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
authors: S
authors: S
authors: Malkani
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01615, USA. Silvia.Corvera@umassmed.edu.
authors: S
authors: S
authors: Corvera
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000098:blood supply* / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000033:anatomy & histology* / Q000187:drug effects*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone