title: Biomarkers of Ectopic Fat Deposition: The Next Frontier in Serum Lipidomics.
abstract: BACKGROUND
  Strong evidence suggests that ectopic fat rather than fat mass per se drives risk for type 2 diabetes. Nonetheless, biomarkers of ectopic fat have gone unexplored.
  
  
  OBJECTIVE
  To determine the utility of serum lipidomics to predict ectopic lipid deposition.
  
  
  METHODS
  Cross-sectional.
  
  
  METHODS
  The Clinical Translational Research Center at the University of Colorado Anschutz Medical Campus.
  
  
  METHODS
  Endurance-trained athletes (n = 15, 41 ± 0.9 y old; body mass index 24 ± 0.6 kg/m(2)) and obese people with or without type 2 diabetes (n = 29, 42 ± 1.4 y old; body mass index 32 ± 2.5 kg/m(2)).
  
  
  METHODS
  Blood sampling and skeletal muscle biopsy.
  
  
  METHODS
  Multivariable models determined the ability of serum lipids to predict intramuscular (im) lipid accumulation of triacylglycerol (TAG), diacylglycerol (DAG), and ceramide (liquid chromatography tandem mass spectroscopy).
  
  
  RESULTS
  Among people with obesity, serum ganglioside C22:0 and lactosylceramide C14:0 predicted muscle TAG (overall model R(2) = 0.48), whereas serum DAG C36:1 and free fatty acid (FFA) C18:4 were strong predictors of muscle DAG (overall model R(2) = 0.77), as were serum TAG C58:5, FFA C14:2 and C14:3, phosphotidylcholine C38:1, and cholesterol ester C24:1 to predict muscle ceramide (overall model R(2) = 0.85). Among endurance-trained athletes, serum FFA C14:1 and sphingosine were significant predictors of muscle TAG (overall model R(2) = 0.81), whereas no models could predict intramuscular DAG or ceramide in this group.
  
  
  CONCLUSIONS
  Different serum lipids predict intramuscular TAG accumulation in obese people vs athletes. The ability of serum lipidomics to predict intramuscular DAG and ceramide in insulin-resistant humans may prove a new biomarker to determine risk for diabetes.
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Leigh
authors.initials: L
authors.lastname: Perreault
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Anne P
authors.initials: AP
authors.lastname: Starling
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Deborah
authors.initials: D
authors.lastname: Glueck
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Brozinick
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Phil
authors.initials: P
authors.lastname: Sanders
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Parker
authors.initials: P
authors.lastname: Siddall
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Ming Shang
authors.initials: MS
authors.lastname: Kuo
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Dana
authors.initials: D
authors.lastname: Dabelea
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (L.P., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; Department of Epidemiology (L.P., A.P.S., D.D.), Colorado School of Public Heath, Aurora, Colorado 80045; Department of Biostatistics and Informatics (D.G.), Colorado School of Public Health, Aurora, Colorado 80045; and Eli Lilly and Company (J.T.B., P.Sa., P.Si., M.S.K.), Indianapolis, Indiana 46285.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Bergman
mesh_terms: D000273:Adipose Tissue; D056352:Athletes; D015415:Biomarkers; D015992:Body Mass Index; D002828:Choristoma / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D055432:Metabolomics; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010807:Physical Endurance; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D008055:Lipids