title: Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness.
abstract: OBJECTIVE
  To identify novel biomarkers through metabolomic profiles that distinguish metabolically well (MW) from metabolically unwell (MUW) individuals, independent of body mass index (BMI).
  
  
  METHODS
  This study was conducted as part of the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) project. Individuals from 3 cohorts were classified as lean (BMI<25kg/m²), overweight (BMI≥25kg/m², BMI<30kg/m²) or obese (BMI≥30kg/m²). Cardiometabolic abnormalities were defined as: (1) impaired fasting glucose (≥100mg/dL and ≤126mg/dL); (2) hypertension; (3) triglycerides ≥150mg/dL; (4) HDL-C <40mg/dL in men, <50mg/dL in women; and (5) insulin resistance (calculated Homeostatic Model Assessment (HOMA-IR) index of >5.13). MW individuals were defined as having <2 cardiometabolic abnormalities and MUW individuals had≥two cardiometabolic abnormalities. Targeted profiling of 55 metabolites used mass-spectroscopy-based methods. Principal components analysis (PCA) was used to reduce the large number of correlated metabolites into clusters of fewer uncorrelated factors.
  
  
  RESULTS
  Of 1872 individuals, 410 were lean, 610 were overweight, and 852 were obese. Of lean individuals, 67% were categorized as MUW, whereas 80% of overweight and 87% of obese individuals were MUW. PCA-derived factors with levels that differed the most between MW and MUW groups were factors 4 (branched chain amino acids [BCAA]) [p<.0001], 8 (various metabolites) [p<.0001], 9 (C4/Ci4, C3, C5 acylcarnitines) [p<.0001] and 10 (amino acids) [p<.0002]. Further, Factor 4, distinguishes MW from MUW individuals independent of BMI.
  
  
  CONCLUSIONS
  BCAA and related metabolites are promising biomarkers that may aid in understanding cardiometabolic health independent of BMI category.
authors: Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC 27710, USA. bryan.batch@duke.edu
authors: Bryan C
authors: BC
authors: Batch
authors: Svati H
authors: SH
authors: Shah
authors: Christopher B
authors: CB
authors: Newgard
authors: Christy B
authors: CB
authors: Turer
authors: Carol
authors: C
authors: Haynes
authors: James R
authors: JR
authors: Bain
authors: Michael
authors: M
authors: Muehlbauer
authors: Mahesh J
authors: MJ
authors: Patel
authors: Robert D
authors: RD
authors: Stevens
authors: Lawrence J
authors: LJ
authors: Appel
authors: L Kristin
authors: LK
authors: Newby
authors: Laura P
authors: LP
authors: Svetkey
mesh_terms: D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001771:Blood Banks; D015992:Body Mass Index; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008659:Metabolic Diseases / Q000097:blood* / Q000150:complications / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000378:metabolism; D050177:Overweight / Q000097:blood* / Q000150:complications / Q000378:metabolism; D025341:Principal Component Analysis; D013851:Thinness / Q000097:blood* / Q000150:complications / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D015415:Biomarkers
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