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Short-Term Manipulation of Plasma Free Fatty Acids Does Not Change Skeletal Muscle Concentrations of Ceramide and Glucosylceramide in Lean and Overweight Subjects

Departments of Endocrinology and Metabolism (M.J.S., E.F., H.P.S.), Medical Biochemistry (A.J.M., J.E.G., J.M.A.), Genetic Metabolic Diseases (M.D.), and Clinical Chemistry (E.E.), Laboratory of Endocrinology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: M.J.M. Serlie, Academic Medical Center F5-169, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: m.j.serlie{at}amc.uva.nl.

Context: Increased plasma free fatty acid (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 FFAs were either increased or decreased for 6 h 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: Eight lean [body mass index 21.9 (range, 19.6–24.6) kg/m²] and six overweight/obese [body mass index 34.4 (27.8–42.5) kg/m²] subjects without type 2 diabetes mellitus participated in the study.

Main Outcome Measure: Differences in muscle ceramide and glucosylceramide upon manipulation of plasma FFAs were measured.

Results: There were no differences in muscle ceramide and glucosylceramide between lean and obese subjects, respectively. Increasing or decreasing plasma FFAs for 6 h had no effect on ceramide [high FFAs: 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, respectively; low FFAs: 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, respectively] and glucosylceramide [high FFAs: 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, respectively; low FFAs: 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, respectively] concentrations in skeletal muscle.

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

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