Context: Increased plasma FFA concentrations may be in part responsible for the increased levels of ceramide in skeletal muscle of obese subjects.

Objective: We studied the effect of lowering and increasing plasma FFA levels on muscle ceramide and glucosylceramide concentrations in lean and obese subjects.

Design: Plasma FFA were either increased or decreased for 6 hours by infusing a lipid emulsion or using Acipimox® respectively. Muscle biopsies were performed before and after the intervention for measurements of ceramide and glucosylceramide.

Study subjects: 8 Lean (BMI 21.9 [19.6-24.6] kg/m²) and 6 overweight/obese (BMI 34.4 [27.8-42.5] kg/m²) subjects without type 2 diabetes mellitus

Main outcome measure: Differences in muscle ceramide and glucosylceramide upon manipulation of plasma FFA

Results: There were no differences in muscle ceramide and glucosylceramide between lean and obese subjects respectively. Increasing or decreasing plasma FFA for 6 hours had no effect on ceramide (High FFA: 24 [19-25] vs.24 [22-27] pmol/mg muscle, p=0.46 and 22 [20-28] vs. 24 [18-26] pmol/mg muscle, p =0.89 in lean and obese resp.; Low FFA: 26 [24-35] vs. 23 [18-27] pmol/mg muscle, p =0.17 and 24 [15-44] vs. 24 [19-42] pmol/mg muscle, p =0.6 in lean and obese resp.) and glucosylceramide (High FFA: 2.0 [1.7-4.3] vs. 3.4 [2.1-4.6] pmol/mg muscle, p = 0.17 and 3.0 [1.3-6.7] vs. 2.6 [1.2-3.9] pmol/mg muscle, p = 0.89 in lean and obese resp.; Low FFA: 2.2 [1.0-4.4] vs. 1.7 [1.4-3.0] pmol/mg muscle, p =0.92 and 6.6 [1.0-25.0] vs. 4.3 [1.3-7.6] pmol/mg muscle, p =0.7 in lean and obese resp.) concentrations in skeletal muscle.

Conclusion: Short-term manipulation of plasma FFA has no effect on ceramide and glucosylceramide concentrations in skeletal muscle from lean and obese subjects.