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Low Adiponectin Levels in Adolescent Obesity: A Marker of Increased Intramyocellular Lipid Accumulation

Department of Pediatrics (R.W., S.E.T., S.C.), The Children’s and Adult Clinical Research Centers of Yale University School of Medicine (A.G., J.D.), Department of Internal Medicine (K.P.), and Howard Hughes Medical Institute (S.D., G.S.), New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Sonia Caprio, M.D., Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208064, New Haven, Connecticut 06520. E-mail: sonia.caprio{at}yale.edu.

We examined the impact of adolescent obesity on circulating adiponectin levels and the relationship between adiponectin and insulin sensitivity, intramyocellular (IMCL) lipid content, plasma triglycerides, and free fatty acids. Plasma adiponectin levels were measured in 8 nonobese (percentage fat, 18 ± 1.8) and 14 obese adolescents (percentage fat, 41 ± 1.6). Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Intramuscular lipid content was quantified using ¹H-nuclear magnetic resonance spectroscopy, and abdominal fat distribution by magnetic resonance imaging. Adiponectin levels were lower in obese adolescents (9.2 ± 1 µg/ml, P < 0.001) and were positively related to insulin sensitivity in all subjects (r = 0.531, P < 0.02). Strong inverse relationships were found between adiponectin and triglyceride levels (r = -0.80, P < 0.001) and IMCL (r = -0.73, P < 0.001). Triglycerides (partial r² = 0.52; P < 0.0002) and IMCL (partial r² = 0.10; P < 0.05) were the most significant predictors of adiponectin levels, explaining 62% of the variation. In conclusion, plasma adiponectin levels are reduced in adolescent obesity and related to insulin resistance, independent of total body fat and central adiposity. There is a strong relationship between adiponectin and IMCL lipid content in this pediatric population. The putative modulatory effects of adiponectin on insulin sensitivity may, in part, be mediated via its effects on IMCL lipid content.

This work was supported by NIH Grants RO1-HD-28016 and RO1-HD-40787 (to S.C.), MO1-RR00125, and MO1-RR06022. S.C. is a recipient of a K24 HD01464 Award for Patient-Oriented Research.

Abbreviations: BMI, Body mass index; EMCL, extramyocellular; FFA, free fatty acid; IMCL, intramyocellular; M, insulin sensitivity; MRI, magnetic resonance imaging; NMR, nuclear magnetic resonance.

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