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.
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 TKRpatients 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: Melissa G Farb; Sherman Bigornia; Melanie Mott; Kahraman Tanriverdi; Kristine M Morin; Jane E Freedman; Lija Joseph; Donald T Hess; Caroline M Apovian; Joseph A Vita; Noyan Gokce Journal: J Am Coll Cardiol Date: 2011-07-12 Impact factor: 24.094
Authors: Gaurav Sharma; Rohan Kulkarni; Samir K Shah; William W King; Alban Longchamp; Ming Tao; Kui Ding; C Keith Ozaki Journal: Surgery Date: 2016-04-14 Impact factor: 3.982
Authors: Gaurav Sharma; Ming Tao; Kui Ding; David Yu; William King; Galina Deyneko; Xiaosong Wang; Alban Longchamp; Frederick J Schoen; C Keith Ozaki; Marcus E Semel Journal: Stroke Date: 2015-05-12 Impact factor: 7.914
Authors: Joan Clària; Binh T Nguyen; Arin L Madenci; C Keith Ozaki; Charles N Serhan Journal: Am J Physiol Cell Physiol Date: 2013-01-30 Impact factor: 4.249
Authors: Alban Longchamp; Ming Tao; Alexander Bartelt; Kui Ding; Lydia Lynch; Christopher Hine; Jean-Marc Corpataux; Bruce S Kristal; James R Mitchell; C Keith Ozaki Journal: Adipocyte Date: 2015-11-20 Impact factor: 4.534
Authors: Gaurav Sharma; Christopher Kuppler; Yong He; Ming Tao; Kui Ding; Alban Longchamp; Laura M Dember; C Keith Ozaki; Scott A Berceli Journal: Kidney Int Rep Date: 2018-03-02