Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes.

Intramuscular triglyceride (IMTG) has received considerable attention as a potential mechanism promoting insulin resistance. Endurance-trained athletes have high amounts of IMTG but are insulin sensitive, suggesting IMTG content alone does not change insulin action. Recent data suggest increased muscle lipid synthesis protects against fat-induced insulin resistance. We hypothesized that rates of IMTG synthesis at rest would be increased in athletes compared with controls. Eleven sedentary men and 11 endurance-trained male cyclists participated in this study. An intravenous glucose tolerance test was performed to assess insulin action. After 3 days of dietary control and an overnight fast, [13C16]palmitate was infused at 0.0174 micromol.kg(-1).min(-1) for 4 h, followed by a muscle biopsy to measure isotope incorporation into IMTG and diacylglycerol. Compared with controls, athletes were twice as insulin sensitive (P=0.004) and had a significantly greater resting IMTG concentration (athletes: 20.4+/-1.6 microg IMTG/mg dry wt, controls: 14.5+/-1.8 microg IMTG/mg dry wt, P=0.04) and IMTG fractional synthesis rate (athletes: 1.56+/-0.37%/h, controls: 0.61+/-0.15%/h, P=0.03). Stearoyl-CoA desaturase 1 mRNA expression (P=0.02) and protein content (P=0.03) were also significantly greater in athletes. Diacylglycerol, but not IMTG, saturation was significantly less in athletes compared with controls (P=0.002). These data indicate endurance-trained athletes have increased synthesis rates of skeletal muscle IMTG and decreased saturation of skeletal muscle diacylglycerol. Increased synthesis rates are not due to recovery from exercise and are likely adaptations to chronic endurance exercise training.

[1]  R. Eckel,et al.  Intramuscular Lipid Metabolism in the Insulin Resistance of Smoking , 2009, Diabetes.

[2]  F. Schick,et al.  Individual Stearoyl-CoA Desaturase 1 Expression Modulates Endoplasmic Reticulum Stress and Inflammation in Human Myotubes and Is Associated With Skeletal Muscle Lipid Storage and Insulin Sensitivity In Vivo , 2009, Diabetes.

[3]  J. Helge,et al.  Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity , 2008, Diabetologia.

[4]  Sarah E. Sauers,et al.  Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited. , 2008, American journal of physiology. Endocrinology and metabolism.

[5]  Hitoshi Shimano,et al.  Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance , 2007, Nature Medicine.

[6]  Yiying Zhang,et al.  Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. , 2007, The Journal of clinical investigation.

[7]  J. Horowitz,et al.  Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. , 2007, The Journal of clinical investigation.

[8]  M. Jensen,et al.  Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high-fat-fed obese rats Published, JLR Papers in Press, September 11, 2006. , 2006, Journal of Lipid Research.

[9]  K. Petersen,et al.  Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction , 2006, Diabetes.

[10]  L. Zhou,et al.  Fatty acids inhibit intramyocellular triglyceride synthesis and turnover acutely in high fat-fed obese rats. , 2006, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[11]  M. Febbraio,et al.  Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro , 2006, Diabetologia.

[12]  G. Heigenhauser,et al.  Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. , 2006, American journal of physiology. Endocrinology and metabolism.

[13]  E. Wagner,et al.  Defective Lipolysis and Altered Energy Metabolism in Mice Lacking Adipose Triglyceride Lipase , 2006, Science.

[14]  N. Alpert,et al.  Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage. , 2006, American journal of physiology. Endocrinology and metabolism.

[15]  R. Bergman Minimal Model: Perspective from 2005 , 2006, Hormone Research in Paediatrics.

[16]  E. Hoffman,et al.  Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. , 2005, Cell metabolism.

[17]  M. Febbraio,et al.  Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle. , 2004, American journal of physiology. Endocrinology and metabolism.

[18]  A. Dobrzyń,et al.  Effect of endurance training on the sphingomyelin-signalling pathway activity in the skeletal muscles of the rat. , 2004, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[19]  M. Jensen,et al.  Accelerated intramyocellular triglyceride synthesis in skeletal muscle of high-fat-induced obese rats , 2003, International Journal of Obesity.

[20]  G. Grunwald,et al.  Comparison of methods for achieving 24-hour energy balance in a whole-room indirect calorimeter. , 2003, Obesity research.

[21]  Robert V Farese,et al.  Triglyceride accumulation protects against fatty acid-induced lipotoxicity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  B. Vessby,et al.  Fatty acid composition of skeletal muscle reflects dietary fat composition in humans. , 2002, The American journal of clinical nutrition.

[23]  Lawrence J Appel,et al.  Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[24]  G. Shulman,et al.  Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects. , 2002, Diabetes.

[25]  M. Jensen,et al.  Determination of skeletal muscle triglyceride synthesis using a single muscle biopsy. , 2002, Metabolism: clinical and experimental.

[26]  Y. Kamei,et al.  Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training. , 2002, Biochemical and biophysical research communications.

[27]  B. Yandell,et al.  Loss of stearoyl–CoA desaturase-1 function protects mice against adiposity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[28]  N. Ruderman,et al.  Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α , 2002 .

[29]  B. Saltin,et al.  Intramuscular fatty acid metabolism in contracting and non‐contracting human skeletal muscle , 2002, The Journal of physiology.

[30]  Simon C Watkins,et al.  Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. , 2001, The Journal of clinical endocrinology and metabolism.

[31]  V. Noé,et al.  DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells. , 2001, American journal of physiology. Endocrinology and metabolism.

[32]  G. Cooney,et al.  Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle. , 2000, American journal of physiology. Endocrinology and metabolism.

[33]  A. Bonen,et al.  Endurance training increases FFA oxidation and reduces triacylglycerol utilization in contracting rat soleus. , 2000, American journal of physiology. Endocrinology and metabolism.

[34]  D. Hachey,et al.  Validation of a new procedure to determine plasma fatty acid concentration and isotopic enrichment. , 1999, Journal of lipid research.

[35]  R. Donnelly,et al.  Tissue and Isoform-selective Activation of Protein Kinase C in Insulin-resistant Obese Zucker Rats – Effects of Feeding , 2022 .

[36]  S. Corbalán-García,et al.  A comparative study of the activation of protein kinase C alpha by different diacylglycerol isomers. , 1999, The Biochemical journal.

[37]  Honglin Zhou,et al.  Regulation of Insulin-Stimulated Glucose Transporter GLUT4 Translocation and Akt Kinase Activity by Ceramide , 1998, Molecular and Cellular Biology.

[38]  E. Richter,et al.  Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans. , 1998, American journal of physiology. Endocrinology and metabolism.

[39]  S. Klein,et al.  Improved accuracy and precision of gas chromatography/mass spectrometry measurements for metabolic tracers. , 1998, Metabolism: clinical and experimental.

[40]  D. Chinkes,et al.  Regional acetate kinetics and oxidation in human volunteers. , 1998, The American journal of physiology.

[41]  M. Jensen,et al.  Intramuscular fatty acid metabolism evaluated with stable isotopic tracers. , 1998, Journal of applied physiology.

[42]  D. Brindley,et al.  Effects of Cell-Permeable Ceramides and Tumor Necrosis Factor-α on Insulin Signaling and Glucose Uptake in 3T3-L1 Adipocytes , 1998, Diabetes.

[43]  S. Lillioja,et al.  Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action , 1997, Diabetes.

[44]  A. Hinderliter,et al.  Activation of protein kinase C by coexisting diacylglycerol-enriched and diacylglycerol-poor lipid domains. , 1997, Biochemistry.

[45]  D. Matthews Radioactive and Stable Isotope Tracers in Biomedicine: Principles and Practice of Kinetic Analysis , 1993 .

[46]  J. Knudsen,et al.  A fast and versatile method for extraction and quantitation of long-chain acyl-CoA esters from tissue: content of individual long-chain acyl-CoA esters in various tissues from fed rat. , 1992, Analytical biochemistry.

[47]  F. A. Kenney,et al.  Heated dorsal hand vein sampling for metabolic studies: a reappraisal. , 1992, The American journal of physiology.

[48]  J. Ivy,et al.  Muscle glucose transport, GLUT-4 content, and degree of exercise training in obese Zucker rats. , 1992, The American journal of physiology.

[49]  E. Kraegen,et al.  Influence of Dietary Fat Composition on Development of Insulin Resistance in Rats: Relationship to Muscle Triglyceride and ω-3 Fatty Acids in Muscle Phospholipid , 1991, Diabetes.

[50]  D. Schoeller,et al.  Inaccuracies in self-reported intake identified by comparison with the doubly labelled water method. , 1990, Canadian journal of physiology and pharmacology.

[51]  D. E. Kerr,et al.  Structural requirements of diacylglycerols for binding and activating phospholipid-dependent, Ca++-sensitive protein kinase. , 1987, Biochemical and biophysical research communications.

[52]  E. Kraegen,et al.  Fish oil prevents insulin resistance induced by high-fat feeding in rats. , 1987, Science.

[53]  D. Costill,et al.  SUBMAXIMAL AND MAXIMAL WORKING CAPACITY OF ELITE DISTANCE RUNNERS. PART II. MUSCLE FIBER COMPOSITION AND ENZYME ACTIVITIES * , 1977, Annals of the New York Academy of Sciences.

[54]  E Hultman,et al.  Diet, muscle glycogen and physical performance. , 1967, Acta physiologica Scandinavica.

[55]  G. Brooks,et al.  Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training. , 2007, American journal of physiology. Endocrinology and metabolism.

[56]  A. Russell Lipotoxicity: the obese and endurance-trained paradox , 2004, International Journal of Obesity.

[57]  N. Ruderman,et al.  Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. , 2002, Diabetes.

[58]  G. Brooks,et al.  Evaluation of exercise and training on muscle lipid metabolism. , 1999, American journal of physiology. Endocrinology and metabolism.

[59]  S A Kautz,et al.  Physiological and biomechanical factors associated with elite endurance cycling performance. , 1991, Medicine and science in sports and exercise.