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Am J Physiol Endocrinol Metab (May 15, 2007). doi:10.1152/ajpendo.00123.2007
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Submitted on February 23, 2007
Accepted on May 8, 2007

Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin resistant adults

Valerie Brid O'Leary1, Ashley E Jorett2, Christine M Marchetti3, Frank Gonzalez4, S.A. Phillips5, T.P. Ciaraldi6, and J.A. Kirwan1*

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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