Serum lipids and sphingolipids circulate in plasma and are linked with insulin resistance and increased cardiovascular disease risk. We previously reported that dihydroceramides (DHCer) are elevated in people with insulin resistance compared to individuals with obesity and trained athletes. Despite associations with insulin resistance, little is known whether insulin sensitizing lifestyle interventions can improve sphingolipid profiles.
Twenty-one individuals with obesity and prediabetes (18F; 46± 2y; 35.0± 0.9 kg/m2; fasting glucose: 113.8± 9.4 mg/dl, 2h OGTT: 143.0± 19.4 mg/dl) participated in a 3-month lifestyle intervention of combined weight loss and exercise. Insulin sensitivity (SI) was assessed by hyperinsulinemic-euglycemic clamps and both targeted and shotgun lipidomics were conducted before and after intervention.
BMI and body fat percentage were reduced by 11+1% (mean± SEM) and 9± 1% after intervention (p<0.0001 for both). VO2 peak and SI increased by 14± 3% and 66± 12% following the intervention (p<0.0001 for both). Total serum triacylglyceride, diacylglyceride, DHCer and glucosylceramide were significantly reduced following intervention (p<0.05 for all). Reductions in specific species of ceramide (C18:0), lactosylceramide (C24:0), DHCer (C18:0, C24:1, C24:0) and glucosylceramide (C16:0, C22:0, C23:0, C24:1, C24:0) were also apparent. Of these lipids, glucosylceramide C20:0 and C22:0 were negatively associated with SI (r=-0.491, p<0.05 and r=-0.580, p<0.01, respectively). Furthermore, sphingomyelin C14:0, C16:1, C20:0, C21:0, C22:0, C23:0, C24:3 and C24:4 were negatively associated with SI.
These data show that serum sphingolipids species previously linked to insulin resistance in humans can be improved with insulin sensitizing lifestyle interventions. Decreases in serum sphingolipids may explain increased SI and decreased cardiovascular disease risk associated with weight loss and exercise training.
J.L. Broussard: Advisory Panel; Self; National Institutes of Health. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Sleep Research Society, Society in Science-The Branco Weiss Fellowship. D.E. Kahn: None. S.A. Newsom: None. J.T. Brozinick: Employee; Self; Eli Lilly and Company. H. Bui: Employee; Self; Eli Lilly and Company. K.D. Roth: Employee; Self; Eli Lilly and Company. L. Perreault: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. B.C. Bergman: Advisory Panel; Spouse/Partner; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc.
American Diabetes Association (1-14-CE-05 to B.B.); National Institutes of Health (RR-00036, K01DK110138); Colorado Nutrition Obesity Research Center (P30DK048520)