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Adipocyte Differentiation-Related Protein and OXPAT in Rat and Human Skeletal Muscle: Involvement in Lipid Accumulation and Type 2 Diabetes Mellitus

NUTRIM School for Nutrition, Toxicology, and Metabolism (R.M., P.S., G.S., J.A.J., E.L., M.K.C.H.), Departments of Human Movement Sciences and Human Biology, Maastricht University Medical Centre+, 6200 MD Maastricht, The Netherlands; and Wageningen University (M.M.), Division of Human Nutrition, 6700 EV Wageningen, The Netherlands

Address all correspondence and requests for reprints to: Matthijs K. C. Hesselink, Ph.D., NUTRIM School for Nutrition, Toxicology, and Metabolism, Department of Human Movement Sciences, Maastricht University Medical Center+, P.O. Box 616, NL-6200 MD Maastricht, The Netherlands. E-mail: matthijs.hesselink{at}bw.unimaas.nl.

Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin, adipocyte differentiation-related protein (ADRP), and TIP47] family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues.

Objective: This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in modulating insulin sensitivity.

Design: Muscle OXPAT and ADRP protein content was examined during the development of insulin resistance in Zucker diabetic fatty (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects. Furthermore, we examined the effect of 8 wk of insulin sensitizing by rosiglitazone on muscle OXPAT and ADRP content.

Results: OXPAT and ADRP protein expression is muscle fiber type specific in humans and rats, with highest protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein content was 2- to 3-fold higher in ZDF rats during the progression of type 2 diabetes than in lean normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL level, was not different between type 2 diabetes patients and control subjects. ADRP content was negatively associated with insulin-stimulated glucose uptake (r = –0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle OXPAT (–29%) and ADRP (–28%) content in diabetes patients, without affecting IMCL.

Conclusions: These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes.