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/m2) men ( n = 7) and women ( n = 14) were randomly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric (ExHypo, ∼500 kcal reduction, n = 11) or eucaloric diet (ExEu, n = 10). Insulin sensitivity was determined by the euglycemic (5.0 mM) hyperinsulinemic (40 mU·m−2·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·kg FFM−1·min−1, and ExEu: 2.9 ± 0.4 vs. 4.1 ± 0.4 mg·kg FFM−1·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.