title: Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults.
abstract: Circulating adiponectin is reduced in disorders associated with insulin resistance. This study was conducted to determine whether an exercise/diet intervention would alter adiponectin multimer distribution and adiponectin receptor expression in skeletal muscle. Impaired glucose-tolerant older (>60 yr) obese (BMI 30-40 kg/m(2)) men (n = 7) and women (n = 14) were randomly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric (ExHypo, approximately 500 kcal reduction, n = 11) or eucaloric diet (ExEu, n = 10). Insulin sensitivity was determined by the euglycemic (5.0 mM) hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp. Adiponectin multimers [high (HMW), middle (MMW), and low molecular weight (LMW)] were measured by nondenaturing Western blot analysis. Relative quantification of adiponectin receptor expression through RT-PCR was determined from skeletal muscle biopsy samples. Greater weight loss occurred in ExHypo compared with ExEu subjects (8.0 +/- 0.6 vs. 3.2 +/- 0.6%, P < 0.0001). Insulin sensitivity improved postintervention in both groups (ExHypo: 2.5 +/- 0.3 vs. 4.4 +/- 0.5 mg x kg FFM(-1) x min(-1), and ExEu: 2.9 +/- 0.4 vs. 4.1 +/- 0.4 mg x kg FFM(-1) x min(-1), P < 0.0001). Comparison of multimer isoforms revealed a decreased percentage in MMW relative to HMW and LMW (P < 0.03). The adiponectin SA ratio (HMW/total) was increased following both interventions (P < 0.05) and correlated with the percent change in insulin sensitivity (P < 0.03). Postintervention adiponectin receptor mRNA expression was also significantly increased (AdipoR1 P < 0.03, AdipoR2 P < 0.02). These data suggest that part of the improvement in insulin sensitivity following exercise and diet may be due to changes in the adiponectin oligomeric distribution and enhanced membrane receptor expression.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Jorett
authors.forename: Christine M
authors.initials: CM
authors.lastname: Marchetti
authors.forename: Frank
authors.initials: F
authors.lastname: Gonzalez
authors.forename: Susan A
authors.initials: SA
authors.lastname: Phillips
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Ciaraldi
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000368:Aged; D004032:Diet; D019281:Dimerization; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000628:therapy*; D010101:Oxygen Consumption; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface