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

Wiley - Tập 13 Số 8 - Trang 1321-1329 - 2005
Susan A. Phillips1,2, Charles Choe3,2, Theodore P. Ciaraldi3,2, Andrew S. Greenberg4, Alice P.S. Kong3,2, Sunita Baxi2, Louis Christiansen3,2, Sunder Mudaliar3,2, Robert R. Henry3,2
1Department of Pediatrics, University of California San Diego, La Jolla, California
2Veterans Affairs San Diego Healthcare System, San Diego, California
3Department of Medicine, University of California, San Diego, La Jolla, California
4Jean Mayer Human Nutrition Research Center at Tufts University, Boston, Massachusetts

Tóm tắt

AbstractObjective: 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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