Adipocyte Differentiation-related Protein in Human Skeletal Muscle: Relationship to Insulin Sensitivity

Authors

  • Susan A. Phillips,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Pediatrics, University of California, San Diego, La Jolla, California
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  • Charles C. Choe,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Medicine, University of California, San Diego, La Jolla, California
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  • Theodore P. Ciaraldi,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Medicine, University of California, San Diego, La Jolla, California
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  • Andrew S. Greenberg,

    1. Jean Mayer Human Nutrition Research Center at Tufts University, Boston, Massachusetts
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  • Alice P. S. Kong,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Medicine, University of California, San Diego, La Jolla, California
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  • Sunita C. Baxi,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
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  • Louis Christiansen,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Medicine, University of California, San Diego, La Jolla, California
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  • Sunder R. Mudaliar,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Medicine, University of California, San Diego, La Jolla, California
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  • Robert R. Henry

    Corresponding author
    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Medicine, University of California, San Diego, La Jolla, California
      VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161. E-mail: rrhenry@vapop.ucsd.edu
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  • The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161. E-mail: rrhenry@vapop.ucsd.edu

Abstract

Objective: To determine whether adipocyte differentiation-related protein (ADRP), a lipid droplet—associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non-diabetic (OND) and obese diabetic (OD) subjects.

Research Methods and Procedures: Ten OND subjects and 15 OD subjects underwent a weight loss or pharmacological intervention program to improve insulin sensitivity. Anthropometric data, hemoglobin A1C, fasting glucose, lipids, and glucose disposal rate were determined at baseline and at completion of studies. Biopsies of the vastus lateralis muscle (SkM) were obtained in the fasting state from OND and OD subjects. Protein expression was determined by Western blotting.

Results: ADRP was highly expressed in SkM from OND (4.4 ± 1.54 AU/10 μg, protein, n = 10) and OD (5.02 ± 1.33 AU/10 μg, n = 12) subjects. OND subjects undergoing weight loss had decreased triglyceride levels and improved insulin action. SkM ADRP content increased with weight loss from 5.14 ± 2.15 AU/10 μg to 9.92 ± 1.57 AU/10 μg (p < 0.025). OD subjects were treated with either troglitazone or metformin, together with glyburide, for 3 to 4 months. Both treatments attained similar levels of glycemic control. OD subjects with lower baseline ADRP content (2.85 ± 1.07 AU/10 μg, n = 6) displayed up-regulation of ADRP expression (to 9.27 ± 2.76 AU/10 μg, p < 0.025).

Discussion: ADRP is the predominant lipid droplet—associated protein in SkM, and low ADRP expression is up-regulated in circumstances of improved glucose tolerance. Up-regulation of ADRP may act to sequester fatty acids as triglycerides in discrete lipid droplets that could protect muscle from the detrimental effects of fatty acids on insulin action and glucose tolerance.

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