title: Serum metabolic biomarkers distinguish metabolically healthy peripherally obese from unhealthy centrally obese individuals.
abstract: BACKGROUND
  Metabolic abnormalities are more associated with central obesity than peripheral obesity, but the underlying mechanisms are largely unknown. The present study was to identify serum metabolic biomarkers which distinguish metabolically unhealthy centrally obese (MUCO) from metabolically healthy peripherally obese (MHPO) individuals.
  
  
  METHODS
  A two-stage case-control study design was employed. In the discovery stage, 20 individuals (10 MHPO and 10 MUCO) were included and in the following validation stage, 79 individuals (20 normal weight (NW), 30 MHPO, 29 MUCO) were utilized. Study groups were matched for age, sex, physical activity and total dietary calorie intake with MHPO and MUCO additionally matched for BMI. Metabolic abnormality was defined as: 1) HOMA-IR > 4.27 (90(th) percentile), 2) high-density lipoprotein cholesterol < 1.03 mmol/L in men and < 1.30 mmol/L in women, 3) fasting blood glucose ≥ 5.6 mmol/L, and 4) waist circumference > 102 cm in men and > 88 cm in women. MUCO individuals had all of these abnormalities whereas MHPO and NW individuals had none of them. A targeted metabolomics approach was performed on fasting serum samples, which can simultaneously identify and quantify 186 metabolites.
  
  
  RESULTS
  In the discovery stage, serum leucine, isoleucine, tyrosine, valine, phenylalanine, alpha-aminoadipic acid, methioninesulfoxide and propionylcarnitine were found to be significantly higher in MUCO, compared with MHPO group after multiple testing adjustment. Significant changes of five metabolites (leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine) were confirmed in the validation stage.
  
  
  CONCLUSIONS
  Significantly higher levels of serum leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine are characteristic of metabolically unhealthy centrally obese patients. The finding provides novel insights into the pathogenesis of metabolic abnormalities in obesity.
authors.affiliation: College of Food Science and Engineering, Ocean University of China, No.5, Yu Shan Road, Qingdao, Shandong Province China ; Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada ; Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000 Liaoning China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Pardis
authors.initials: P
authors.lastname: Pedram
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Farrell
authors.initials: F
authors.lastname: Cahill
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Randell
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Wayne
authors.initials: W
authors.lastname: Gulliver
authors.affiliation: Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John's, NL Canada.
authors.forename: Guang
authors.initials: G
authors.lastname: Sun
keywords: Biomarkers; Healthy peripheral obesity; Human; Metabolomics; Serum; Unhealthy central obesity