title: Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans.
abstract: BACKGROUND
  Mouse studies suggest that adropin, a peptide hormone, is required for metabolic homeostasis and prevention of obesity-associated insulin resistance. Whether obesity and insulin resistance are associated with low plasma adropin levels in humans is not known.
  
  
  OBJECTIVE
  Our objective was to investigate the hypothesis that obesity and indicators of insulin resistance are associated with low adropin levels and determine whether weight loss regulates adropin levels.
  
  
  METHODS
  Plasma was obtained from 85 female [age 21-67 yr, body mass index (BMI) 19.4-71.5 kg/m2] and 45 male (age 18-70 yr, BMI 19.1-62.6 kg/m2) volunteers for other clinical studies. The impact of Roux-en-Y gastric bypass was investigated in 19 obese females (BMI 37-65 kg/m2) using samples collected at baseline and 1-12 months after surgery.
  
  
  RESULTS
  Adropin levels correlate negatively with BMI (r=-0.335, P<0.001) and age (r=-0.263, P=0.003). Age-adjusted adropin levels are higher in males [4.1 ng/ml; 95% confidence interval (CI)=3.6-4.6 ng/ml] than females (3.0 ng/ml; 95% CI=2.6-3.4 ng/ml) (P=0.001). In all subjects, lower age-adjusted adropin levels were observed in overweight (3.3 ng/ml; 95% CI=2.8-3.8 ng/ml, P=0.033) and obese (2.7 ng/ml; 95% CI=2.1-3.3 ng/ml, P=0.001) compared with healthy-weight subjects (4.1 ng/ml; 95% CI=3.6-4.5 ng/ml). This effect was gender specific (weight category×gender, P<0.001) and was observed in males only. Aging and diagnosis with two or more metabolic syndrome risk factors was associated with low adropin levels, irrespective of sex. Adropin concentrations increased after Roux-en-Y gastric bypass, peaking 3 months after surgery (P<0.01).
  
  
  CONCLUSIONS
  Although males exhibit higher adropin levels that are reduced by obesity, aging and markers of insulin resistance are associated with low plasma adropin irrespective of sex.
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA. abutler@scripps.edu
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Butler
authors.forename: Charmaine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Kimber L
authors.initials: KL
authors.lastname: Stanhope
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Wolfe
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Ali
authors.forename: Majella
authors.initials: M
authors.lastname: O'Keeffe
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: St-Onge
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Havel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D050171:Dyslipidemias / Q000453:epidemiology / Q000378:metabolism; D005260:Female; D015390:Gastric Bypass; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008659:Metabolic Diseases / Q000453:epidemiology* / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism / Q000601:surgery; D010455:Peptides; D011184:Postoperative Period; D012307:Risk Factors; D017678:Sex Distribution; D055815:Young Adult
chemical_list: D001798:Blood Proteins; C568440:Enho protein, human; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides