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1 Department of Pathobiology, Lerner Research Institute, Cleveland, Ohio, United States
2 Department of Physiology, Case Western Reserve University, Cleveland, Ohio, United States
3 Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio, United States
4 Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, United States
5 Division of Pediatric Endocrinology, University of California, San Diego, California, United States
6 Division of Diabetes, Endocrinology and Metabolism, VA San Diego Health Care System, San Diego, California, United States
* To whom correspondence should be addressed. E-mail: kirwanj{at}ccf.org.
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 years) obese (BMI, 30-40 kg.m2) men (n=7) and women (n=14) were randomly assigned to 12 weeks of supervised aerobic exercise combined with either a hypocaloric (ExHypo, ~500 kcal reduction, N=11) 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, middle and low molecular weight, HMW, MMW and LMW, respectively) were measured by non-denaturing 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 to ExEu subjects (8.0 ± 0.6%, versus 3.2 ± 0.6%, p<0.0001). Insulin sensitivity improved post intervention in both groups, (ExHypo: 2.5 ± 0.3 vs. 4.4 ± 0.5, and ExEu: 2.9 ± 0.4 vs. 4.1 ± 0.4 mg.kg-1FFM.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). Post intervention 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.
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