title: Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans.
abstract: Ceramides 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 h at 50% V̇o2 max) 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, and 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 not the total concentrations of either of them, were positively correlated with markers of muscle NF-κB activation, suggesting that specific species activate intracellular inflammation. Interestingly, a subset of sphingomyelin species, notably C14:0, C22:3, and C24:4 species, was positively associated with insulin secretion and glucose tolerance. Together, these data show that unique ceramide and sphingolipid species associate with either protective or deleterious features for diabetes and could provide novel therapeutic targets for the future.
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Bryan.Bergman@ucdenver.edu.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Bergman
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Brozinick
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado; and.
authors.forename: Allison
authors.initials: A
authors.lastname: Strauss
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado; and.
authors.forename: Samantha
authors.initials: S
authors.lastname: Bacon
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Kerege
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Hai Hoang
authors.initials: HH
authors.lastname: Bui
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Phil
authors.initials: P
authors.lastname: Sanders
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Parker
authors.initials: P
authors.lastname: Siddall
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Ming Shang
authors.initials: MS
authors.lastname: Kuo
authors.affiliation: University of Colorado Anschutz Medical Campus, Aurora, Colorado; and.
authors.forename: Leigh
authors.initials: L
authors.lastname: Perreault
mesh_terms: D000328:Adult; D056352:Athletes; D001786:Blood Glucose / Q000378:metabolism; D002518:Ceramides / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism; D010807:Physical Endurance / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology; D057185:Sedentary Behavior; D013107:Sphingolipids / Q000097:blood*
chemical_list: D001786:Blood Glucose; D002518:Ceramides; D013107:Sphingolipids
keywords: athlete's paradox; insulin sensitivity; lipid composition; plasma biomarkers