title: Exercise-induced lowering of fetuin-A may increase hepatic insulin sensitivity.
abstract: BACKGROUND
  Fetuin-A is a novel hepatokine, and there is preliminary evidence that it may contribute to the pathogenesis of type 2 diabetes. Exercise reduces fetuin-A, but the specific metabolic effects particularly as they relate to the regulation of insulin resistance are unknown. This led us to examine the effect of exercise training on circulating fetuin-A in relation to skeletal muscle and/or hepatic insulin resistance in obese adults.
  
  
  METHODS
  Twenty older adults (66.3 ± 0.9 yr; body mass index, 34.1 ± 1.2 kg · m(-1)) participated in this prospective 12-wk study and underwent supervised exercise training (5 d · wk(-1), 60 min · d(-1) at approximately 85% HRmax). Insulin resistance was assessed using the euglycemic-hyperinsulinemic clamp (40 mU · m(-2) · min(-1)) with isotope dilution ([6,6-H2]-glucose). Skeletal muscle insulin sensitivity (rate of glucose disposal), hepatic insulin resistance (rate of glucose appearance × fasting insulin), metabolic flexibility (respiratory quotient clamp - respiratory quotient fasting), fetuin-A, high-molecular weight adiponectin, high-sensitivity C-reactive protein, leptin, and body fat (dual energy x-ray absorptiometry) were measured before and after the intervention.
  
  
  RESULTS
  Exercise reduced body fat, high-sensitivity C-reactive protein, leptin and hepatic as well as skeletal muscle insulin resistance (each, P < 0.05). Fetuin-A was decreased by approximately 8% (pre, 1.01 ± 0.08, vs post, 0.89 ± 0.06 g · L(-1); P < 0.05) after the intervention, and lower fetuin-A after exercise correlated with lower hepatic insulin resistance (r = -0.46, P < 0.01), increased metabolic flexibility (r = -0.70, P < 0.01) and high-molecular weight adiponectin (r = -0.57, P < 0.01).
  
  
  CONCLUSIONS
  Fetuin-A may contribute to exercise training-induced improvements in hepatic insulin resistance, CHO utilization, and inflammation in older obese adults. Further work is required to determine the cellular mechanism(s) of action for fetuin-A because this hepatokine is related to type 2 diabetes risk.
authors.affiliation: 1Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; 2Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH; and 3Metabolic Translational Research Center, Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Malin
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: del Rincon
authors.forename: Hazel
authors.initials: H
authors.lastname: Huang
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D050218:Body Fat Distribution; D002097:C-Reactive Protein / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D020738:Leptin; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein