Serum sphingolipids - relationships to insulin sensitivity and changes with exercise in humans


Ceramide and sphingolipids are a family of lipid molecules that circulate in serum and accumulate in skeletal muscle promoting insulin resistance. Plasma ceramide and dihydroceramide are related to insulin resistance, yet less is known regarding other ceramide and sphingolipid species. Despite its association with insulin sensitivity, chronic endurance exercise training does not change plasma ceramide and sphingolipid content, with little known regarding a single bout of exercise. We measured basal relationships and the effect of acute exercise (1.5 hours at 50% VO2max) and recovery on serum ceramide and sphingolipid content in sedentary obese individuals, endurance-trained athletes, and individuals with type 2 diabetes (T2D). Basal serum C18:0, C20:0, C24:1 ceramide, and C18:0 and total dihydroceramide were significantly higher in T2D, and along with C16:0 ceramide and C18:0 sphingomyelin correlated positively with insulin resistance. Acute exercise significantly increased serum ceramide, glucosylceramide, and GM3 gangliosides which largely decreased to basal values in recovery. Sphingosine-1-phosphate and sphingomyelin did not change during exercise but decreased below basal values in recovery. Serum C16:0 and C18:0 ceramide and C18:0 sphingomyelin, but total concentration of neither, were positively correlated with markers of muscle NFkB activation suggesting specific species activate intracellular inflammation. Interestingly, a subset of sphingomyelin species, notably C14:0, C22:3, and C24:4 species, were positively associated with insulin secretion and glucose tolerance. Together, these data show unique ceramide and sphingolipid species associate with either protective or deleterious features for diabetes, and could provide novel therapeutic targets for the future.

Autor / Fonte:Bryan C Bergman, Joseph T Brozinick, Allison Strauss, Samantha Bacon, Anna Kerege, Hai Hoang Bui, Phil Sanders, Parker Siddall, Ming Shang Kuo, Leigh Perreault American Journal of Physiology. Endocrinology and Metabolism 2015 June 30, : ajpendo.00134.2015