Augmenting muscle diacylglycerol and triacylglycerol content by blocking fatty acid oxidation does not impede insulin sensitivity

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 29, 2012, Pages 11711-11716

  Timmers, Silvie ^a,b   Nabben, Miranda ^b   Bosma, Madeleen ^b   Van Bree, Bianca ^b   Lenaers, Ellen ^b   Van Beurden, Denis ^a,b   Schaart, Gert ^b   Westerterp Plantenga, Margriet S ^b   Langhans, Wolfgang ^b   Hesselink, Matthijs K C ^b   Schrauwen Hinderling, Vera B ^c   Schrauwen, Patrick ^a,b  

^a TOP INSTITUTE FOOD AND NUTRITION   (Netherlands)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CARBONYL CYANIDE 4 (TRIFLUOROMETHOXY)PHENYLHYDRAZONE; CARNITINE; CARNITINE PALMITOYLTRANSFERASE I; DIACYLGLYCEROL; ETOMOXIR; GLUCOSE; GLUCOSE TRANSPORTER 4; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; PLACEBO; PROTEIN KINASE B; TRIACYLGLYCEROL;

ANIMAL EXPERIMENT; ARTICLE; CELL FUNCTION; CONTROLLED STUDY; ENERGY EXPENDITURE; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FATTY ACID OXIDATION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE OXIDATION; HUMAN; HUMAN TISSUE; IN VIVO STUDY; INSULIN BLOOD LEVEL; INSULIN SENSITIVITY; LIPID STORAGE; MALE; MITOCHONDRIAL RESPIRATION; MUSCLE BIOPSY; MYOTUBE; NONHUMAN; NORMAL HUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN CONTENT; PROTEIN LOCALIZATION; SARCOLEMMA; SARCOPLASM; SIGNAL TRANSDUCTION; SKELETAL MUSCLE;

ANALYSIS OF VARIANCE; ANIMALS; BLOTTING, WESTERN; DIGLYCERIDES; EPOXY COMPOUNDS; FATTY ACIDS; FLUORESCENT ANTIBODY TECHNIQUE; GLUCOSE TRANSPORTER TYPE 4; HUMANS; INSULIN RESISTANCE; MALE; MICE; MICE, INBRED C57BL; MITOCHONDRIA; MUSCLE FIBERS, SKELETAL; OXIDATION-REDUCTION; SARCOLEMMA; TRIGLYCERIDES;

MUS;

EID: 84863944529     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1206868109     Document Type: Article

References (39)

1. Boden G, Lebed B, Schatz M, Homko C, Lemieux S (2001) Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects. Diabetes 50:1612-1617. (Pubitemid 33639602)
2. Bachmann OP, et al. (2001) Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans. Diabetes 50:2579-2584. (Pubitemid 33642777)
3. DeFronzo RA, et al. (1981) The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30:1000-1007.
4. Baron AD, Brechtel G, Wallace P, Edelman SV (1988) Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am J Physiol 255: E769-E774.
5. Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789.
6. Hübinger A, Knode O, Susanto F, Reinauer H, Gries FA (1997) Effects of the carnitine-acyltransferase inhibitor etomoxir on insulin sensitivity, energy expenditure and substrate oxidation in NIDDM. Horm Metab Res 29:436-439. (Pubitemid 27454111)
7. Hübinger A, Weikert G, Wolf HP, Gries FA (1992) The effect of etomoxir on insulin sensitivity in type 2 diabetic patients. Horm Metab Res 24:115-118.
8. Barnett M, Collier GR, O'Dea K (1992) The longitudinal effect of inhibiting fatty acid oxidation in diabetic rats fed a high fat diet. Horm Metab Res 24:360-362.
9. Barnett M, Habito R, Cameron-Smith D, Yamamoto A, Collier GR (1996) The effect of inhibiting fatty acid oxidation on basal glucose metabolism in Psammomys obesus. Horm Metab Res 28:165-170. (Pubitemid 26156802)
10. Phielix E, Mensink M (2008) Type 2 diabetes mellitus and skeletal muscle metabolic function. Physiol Behav 94:252-258. (Pubitemid 351615433)
11. Colberg SR, Simoneau JA, Thaete FL, Kelley DE (1995) Skeletal muscle utilization of free fatty acids in women with visceral obesity. J Clin Invest 95:1846-1853.
12. Kelley DE, Simoneau JA (1994) Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J Clin Invest 94:2349-2356.
13. Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106:171-176.
14. Timmers S, Schrauwen P, de Vogel J (2008) Muscular diacylglycerol metabolism and insulin resistance. Physiol Behav 94:242-251. (Pubitemid 351615425)
15. Phielix E, et al. (2008) Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients. Diabetes 57:2943-2949.
16. Kelley DE, He J, Menshikova EV, Ritov VB (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51:2944-2950.
17. Declercq PE, et al. (1987) Characterization of the mitochondrial carnitine palmitoyltransferase enzyme system. I. Use of inhibitors. J Biol Chem 262:9812-9821.
18. Agius L, Meredith EJ, Sherratt HS (1991) Stereospecificity of the inhibition by etomoxir of fatty acid and cholesterol synthesis in isolated rat hepatocytes. Biochem Pharmacol 42:1717-1720.
19. Hinderling VB, Schrauwen P, Langhans W, Westerterp-Plantenga MS (2002) The effect of etomoxir on 24-h substrate oxidation and satiety in humans. Am J Clin Nutr 76: 141-147. (Pubitemid 34686559)
20. Itani SI, Ruderman NB, Schmieder F, Boden G (2002) Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51:2005-2011. (Pubitemid 34729001)
21. Hardie DG (2011) Sensing of energy and nutrients by AMP-activated protein kinase. Am J Clin Nutr 93:891S-896S.
22. Zhang BB, Zhou G, Li C (2009) AMPK: An emerging drug target for diabetes and the metabolic syndrome. Cell Metab 9:407-416.
23. Koves TR, et al. (2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7:45-56.
24. Bouzakri K, et al. (2008) Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle. Diabetes 57:1508-1516.
25. Zick Y (2004) Uncoupling insulin signalling by serine/threonine phosphorylation: A molecular basis for insulin resistance. Biochem Soc Trans 32:812-816.
26. Gamble J, Lopaschuk GD (1997) Insulin inhibition of 5′ adenosine monophosphate-activated protein kinase in the heart results in activation of acetyl coenzyme A carboxylase and inhibition of fatty acid oxidation. Metabolism 46:1270-1274. (Pubitemid 27473509)
27. Beauloye C, et al. (2001) Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides. FEBS Lett 505:348-352. (Pubitemid 32905475)
28. Towler MC, Hardie DG (2007) AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res 100:328-341.
29. Karlsson HK, et al. (2005) Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects. Diabetes 54: 1692-1697. (Pubitemid 40770759)
30. Jakobsen SN, Hardie DG, Morrice N, Tornqvist HE (2001) 5′-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5- aminoimidazole-4-carboxamide riboside. J Biol Chem 276:46912-46916.
31. Timmers S, et al. (2011) Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. PLoS ONE 6:e14503.
32. Amati F, Dube JJ, Coen PM, Goodpaster BH (2009) Diacylglycerol and ceramide content in skeletal muscle insulin resistance: The next chapter in the story of good and bad lipids? Obesity (Silver Spring) 17(Supplement 2):S71.
33. Schrauwen P, et al. (2002) Etomoxir-induced increase in UCP3 supports a role of uncoupling protein 3 as a mitochondrial fatty acid anion exporter. FASEB J 16: 1688-1690.
34. Bergstrom J (1975) Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest 35:609-616.
35. Borghouts LB, Schaart G, Hesselink MK, Keizer HA (2000) GLUT-4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study. Pflugers Arch 441:351-358. (Pubitemid 32128177)
36. Koopman R, Schaart G, Hesselink MK (2001) Optimisation of oil red O staining permits combination with immunofluorescence and automated quantification of lipids. Histochem Cell Biol 116:63-68. (Pubitemid 32695819)
37. Sparks LM, et al. (2011) Remodeling lipid metabolism and improving insulin responsiveness in human primary myotubes. PLoS ONE 6:e21068.
38. Nabben M, et al. (2008) The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice. FEBS Lett 582:4147-4152.
39. den Hoed M, Hesselink MK, van Kranenburg GP, Westerterp KR (2008) Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity. J Appl Physiol 105:561-568.