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Circulating Adiponectin and Expression of Adiponectin Receptors in Human Skeletal Muscle: Associations with Metabolic Parameters and Insulin Resistance and Regulation by Physical Training

Junior Research Group N03, Interdisciplinary Center for Clinical Research Leipzig (M.B., S.K., M.F., N.K.), Department of Surgery (M.R.S.), University of Leipzig, Leipzig, Germany; Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center (J.N.), D-04103 Leipzig, Germany; and Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School (J.W.B., J.H.L., C.J.W., C.S.M.), Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Dr. Christos S. Mantzoros, Division of Endocrinology, ST 816, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215. E-mail: cmantzor{at}bidmc.harvard.edu.

Context: Adiponectin, an adipocyte-secreted hormone, is associated with insulin resistance and the metabolic syndrome.

Objective: The physiological regulation of circulating adiponectin levels and mRNA expression of its receptors (AdipoR1 and AdipoR2) in skeletal muscle remains to be fully elucidated.

Design/Patients: We assessed circulating adiponectin and AdipoR1/R2 mRNA expression in human skeletal muscle in a cross-sectional study of 140 subjects with normal or impaired glucose tolerance or type 2 diabetes. In the context of an interventional study, the same measurements were performed in 60 of these subjects (20/glucose tolerance group) before and after 4 wk of physical training. Finally, we measured these same variables in addition to protein levels of AMP kinase (AMPK), acetyl phosphorylated AMPK, coenzyme A carboxylase, phosphorylated coenzyme A carboxylase, and phosphatidylinositol 3-kinase in muscle before and after 3 h of intensive exercise in a subgroup of five subjects.

Setting: This study was performed at an academic clinical research center.

Results: Circulating adiponectin was negatively associated, whereas AdipoR1/R2 mRNA levels were positively associated with obesity, glucose and lipid levels, and insulin resistance. Physical training for 4 wk resulted in increased circulating adiponectin levels and AdipoR1/R2 mRNA expression in muscle. Exercise for 3 h increased AdipoR1/R2 mRNA expression as well as phosphorylation of AMPK and acetyl coenzyme A carboxylase in muscle, but had no effect on circulating adiponectin.

Conclusions: Adiponectin, AdipoR1, and AdipoR2 are all associated with body composition, insulin sensitivity, and metabolic parameters. Physical training increases circulating adiponectin and mRNA expression of its receptors in muscle, which may mediate the improvement of insulin resistance and the metabolic syndrome in response to exercise.

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