title: Inflammatory "adiposopathy" in major amputation patients.
abstract: BACKGROUND
  Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation.
  
  
  METHODS
  AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression.
  
  
  RESULTS
  Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive.
  
  
  CONCLUSIONS
  AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Mauro
authors.forename: Binh T
authors.initials: BT
authors.lastname: Nguyen
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Ming
authors.initials: M
authors.lastname: Tao
authors.forename: Ian
authors.initials: I
authors.lastname: Gao
authors.forename: Michael A
authors.initials: MA
authors.lastname: Seidman
authors.forename: Louis L
authors.initials: LL
authors.lastname: Nguyen
authors.forename: C Keith
authors.initials: CK
authors.lastname: Ozaki
mesh_terms: D000367:Age Factors; D000368:Aged; D000671:Amputation, Surgical; D019645:Arthroplasty, Replacement, Knee; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000276:immunology; D016022:Case-Control Studies; D002908:Chronic Disease; D015897:Comorbidity; D016207:Cytokines / Q000032:analysis*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000276:immunology; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000276:immunology*; D018836:Inflammation Mediators / Q000032:analysis*; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D020738:Leptin / Q000032:analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000276:immunology; D016491:Peripheral Vascular Diseases / Q000453:epidemiology / Q000276:immunology / Q000601:surgery*; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D019338:Polypharmacy; D011446:Prospective Studies; D052243:Resistin / Q000032:analysis; D012737:Sex Factors; D050151:Subcutaneous Fat / Q000276:immunology*
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; C499624:RETN protein, human; D052243:Resistin; C051321:SERPINE1 protein, human