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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #185613
Title: ADIPOCYTE DIFFERENTIATION-RELATED PROTEIN IN HUMAN SKELETAL MUSCLE: RELATIONSHIP TO INSULIN SENSITIVITY

Author
item PHILLIPS, SUSAN - UNIV CALIFORNIA SAN DIEGO
item CHOE, CHARLES - UNIV CALIFORNIA SAN DIEGO
item CIARALDI, THEODORE - UNIV CALIFORNIA SAN DIEGO
item Greenberg, Andrew
item KONG, ALICE - UNIV CALIFORNIA SAN DIEGO
item BAXI, SUNITA - UNIV CALIFORNIA SAN DIEGO
item CHRISTIANSEN, LOUIS - UNIV CALIFORNIA SAN DIEGO
item MUDALIAR, SUNDER - UNIV CALIFORNIA SAN DIEGO
item HENRY, ROBERT - UNIV CALIFORNIA SAN DIEGO

Submitted to: Obesity Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/16/2005
Publication Date: 8/1/2005
Citation: Phillips, S.A., Choe, C.C., Ciaraldi, T.P., Greenberg, A.S., Kong, A.P., Baxi, S.C., Christiansen, L., Mudaliar, S.R., Henry, R.R. 2005. Adipocyte differentiation-related protein in human skeletal muscle: relationship to insulin sensitivity. Obesity Research. 13(8):1321-1329.

Interpretive Summary: To determine whether a protein related to fat cell differentiation, called ADRP, is 1) expressed in human skeletal muscle and 2) regulated in human skeletal muscle obtained from obese non-diabetic and obese diabetic subjects. Ten obese non-diabetic subjects and 15 obese type 2 diabetic subjects participated in either a weight loss or pharmacological intervention program to improve their sensitivity to insulin. Samples of skeletal muscle were obtained in the fasting state from both obese non-diabetic and obese diabetic subjects. A protein mainly expressed in fat cells, called perilipin, was detectable in skeletal muscle only at low levels. ADRP was not found in fat cell debris produced by cell death but it was highly abundant in skeletal muscle. ADRP expression was similar in skeletal muscle from non-diabetic and type 2 diabetic subjects. Non-diabetic subjects undergoing a caloric restriction weight loss regimen showed improvements in circulating triglyceride levels and whole body insulin action, and ADRP content of the skeletal muscle increased with weight loss. An increase in ADRP expression occurred in six of seven subjects, with no change in the individual with the highest pretreatment value. Obese diabetic subjects with lower baseline ADRP content displayed an increase of ADRP expression. For individuals with the highest pretreatment ADRP expression, treatment had no effect. ADRP is the main lipid droplet-associated protein present in skeletal muscle; low ADRP expression is up-regulated in circumstances of improved glucose tolerance. In discrete lipid droplets, increased expression of ADRP may act to sequester fatty acids as triglycerides. This could protect muscle from the unfavorable effects of fatty acids on insulin action and glucose tolerance.

Technical Abstract: 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. 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. 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). 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.