Journal
OBESITY RESEARCH
Volume 13, Issue 8, Pages 1321-1329Publisher
NORTH AMER ASSOC STUDY OBESITY
DOI: 10.1038/oby.2005.160
Keywords
human; intramyocellular lipid; insulin resistance; skeletal muscle; fat metabolism
Categories
Funding
- NCRR NIH HHS [M01 RR-00827] Funding Source: Medline
- NIDDK NIH HHS [K08 DK-61987, R01 DK-58291, 2 R01 DK50647] Funding Source: Medline
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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 A(1C), 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 mu g, protein, n = 10) and OD (5.02 +/- 1.33 AU/10 mu g, 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 mu g to 9.92 +/- 1.57 AU/10 mu g (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 mu g, n = 6) displayed up-regulation of ADRP expression (to 9.27 +/- 2.76 AU/10 mu g, p < 0.025). Discussion: ADRP is the predominant lipid droplet-associated protein in SkM, and low ADRP expression is upregulated 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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