Adipocyte differentiation-related protein in human skeletal muscle: relationship to insulin sensitivity.
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.


METHODS
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 microg, protein, n = 10) and OD (5.02 +/- 1.33 AU/10 microg, 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 microg to 9.92 +/- 1.57 AU/10 microg (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 microg, n = 6) displayed up-regulation of ADRP expression (to 9.27 +/- 2.76 AU/10 microg, p < 0.025).


CONCLUSIONS
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.
Phillips
Susan A
SA
Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
Choe
Charles C
CC
Ciaraldi
Theodore P
TP
Greenberg
Andrew S
AS
Kong
Alice P S
AP
Baxi
Sunita C
SC
Christiansen
Louis
L
Mudaliar
Sunder R
SR
Henry
Robert R
RR
D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism; D000070780:Perilipin-2
D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2