Leigh Perreault1, Anne P Starling1, Deborah Glueck1, Joseph T Brozinick1, Phil Sanders1, Parker Siddall1, Ming Shang Kuo1, Dana Dabelea1, Bryan C Bergman1. 1. 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.
Abstract
CONTEXT: 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. DESIGN: Cross-sectional. SETTING: The Clinical Translational Research Center at the University of Colorado Anschutz Medical Campus. PARTICIPANTS: 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)). INTERVENTION: Blood sampling and skeletal muscle biopsy. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN: Cross-sectional. SETTING: The Clinical Translational Research Center at the University of Colorado Anschutz Medical Campus. PARTICIPANTS: Endurance-trained athletes (n = 15, 41 ± 0.9 y old; body mass index 24 ± 0.6 kg/m(2)) and obesepeople with or without type 2 diabetes (n = 29, 42 ± 1.4 y old; body mass index 32 ± 2.5 kg/m(2)). INTERVENTION: Blood sampling and skeletal muscle biopsy. MAIN OUTCOME MEASURES: 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 obesepeople 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.
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