title: Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation.
abstract: BACKGROUND
  Heart failure (HF) is characterized by inflammation, insulin resistance, and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated with impaired adipokine signaling and that hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation and correct adipokine signaling in advanced HF.
  
  
  RESULTS
  Circulating insulin, adiponectin, leptin, and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy control subjects. Serum adiponectin was higher in HF patients before VAD implantation compared with control subjects (13.3±4.9 versus 6.4±2.1 μg/mL, P=0.02). VAD implantation (mean, 129±99 days) reduced serum adiponectin (7.4±3.4 μg/mL, P<0.05) and improved insulin resistance (Homeostasis Assessment Model of insulin resistance: 7.6±7.7-4.5±3.6; P=0.012). [corrected] Adiponectin expression in adipose tissue decreased after VAD implantation (-65%; P<0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared with control subjects and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared with control subjects (2105±585 μm(2) [corrected] versus 5583±142 μm(2) in control subjects; P<0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared with control subjects (+25%; P<0.01), which normalized after VAD implantation.
  
  
  CONCLUSIONS
  Adipose tissue inflammation and adiponectin resistance develop in advanced HF. Mechanical unloading of the failing myocardium reverses adipose tissue macrophage infiltration, inflammation, and adiponectin resistance in patients with advanced HF.
authors.affiliation: Division of Preventive Medicine and Nutrition, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Raffay S
authors.initials: RS
authors.lastname: Khan
authors.forename: Tomoko S
authors.initials: TS
authors.lastname: Kato
authors.forename: Aalap
authors.initials: A
authors.lastname: Chokshi
authors.forename: Michael
authors.initials: M
authors.lastname: Chew
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Yu
authors.forename: Christina
authors.initials: C
authors.lastname: Wu
authors.forename: Parvati
authors.initials: P
authors.lastname: Singh
authors.forename: Faisal H
authors.initials: FH
authors.lastname: Cheema
authors.forename: Hiroo
authors.initials: H
authors.lastname: Takayama
authors.forename: Collette
authors.initials: C
authors.lastname: Harris
authors.forename: Gissette
authors.initials: G
authors.lastname: Reyes-Soffer
authors.forename: Ralph
authors.initials: R
authors.lastname: Knöll
authors.forename: Hendrik
authors.initials: H
authors.lastname: Milting
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Naka
authors.forename: Donna
authors.initials: D
authors.lastname: Mancini
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*; D006353:Heart-Assist Devices; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D052243:Resistin / Q000097:blood; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D052243:Resistin