2 Setting: A disordered lipid metabolism is implicated in the development of skeletal muscle insulin resistance.

3 Lipid droplet proteins of the PAT (Perilipin, ADRP - Adipocyte differentiation-related protein – and TIP47)

4 family have been shown to regulate lipid accumulation and intracellular metabolism in other tissues.

5 Objective: This study aimed to explore the role of the PAT proteins OXPAT and ADRP in skeletal muscle

6 lipid metabolism and their putative role in modulating insulin sensitivity.

7 Design: Muscle OXPAT and ADRP protein content was examined during the development of insulin

8 resistance in Zucker diabetic fatty (ZDF) rats, and in type 2 diabetes patients and BMI-matched control

9 subjects. Furthermore, we examined the effect of 8 weeks of insulin sensitizing by rosiglitazone on muscle

10 OXPAT and ADRP content.

11 Results: OXPAT and ADRP protein expression is muscle fiber-type specific in humans and rats, with highest

12 protein content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT and ADRP protein

13 content was 2-3 fold higher in ZDF rats during the progression of type 2 diabetes than in lean

14 normoglycemic control rats, which was paralleled by high IMCL levels. Muscle OXPAT and ADRP content,

15 as well as IMCL level, were not different between type 2 diabetes patients and control subjects. ADRP

16 content was negatively associated with insulin-stimulated glucose uptake (r -0.50, P 0.017). Interestingly,

17 rosiglitazone treatment decreased muscle OXPAT (-29%) and ADRP (-28%) content in diabetes patients,

18 without affecting IMCL.

19 Conclusions: These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and

20 type 2 diabetes.