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PMID: 17510709 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance.

The Journal of clinical investigation ·Vol. 117 ·No. 6 ·2007-06-00 ·Pages 1690-8

Schenk S, Horowitz JF

Abstract

Fatty acid oversupply is a key mediator of skeletal muscle insulin resistance in obesity, primarily via accumulation of fatty acid metabolites and activation of proinflammatory pathways. Herein, we demonstrate that fatty acid-induced insulin resistance in humans is completely prevented the day after 1 session of endurance exercise. Because skeletal muscle is the primary site for systemic glucose disposal and is highly susceptible to impaired insulin action by elevated fatty acid availability, we obtained skeletal muscle samples to investigate possible mechanisms mediating this protective effect of exercise. Prevention of fatty acid-induced insulin resistance after exercise accompanied enhanced skeletal muscle protein expression of key lipogenic enzymes and an increase in muscle triglyceride synthesis. Partitioning more fatty acids toward triglyceride synthesis within muscle reduced the accumulation of fatty acid metabolites and suppressed the proinflammatory response in skeletal muscle, as evidenced by decreased phosphorylation and activation of JNK and increased abundance of inhibitor of NF-kappaB alpha (I kappa B-alpha) and I kappa B-beta. We believe this is the first study to demonstrate that 1 session of exercise completely reverses fatty acid-induced insulin resistance in humans. Reversal of insulin resistance accompanied enhanced lipogenic capacity within skeletal muscle, reduced accumulation of highly bioactive fatty acid metabolites, and suppressed activation of proinflammatory pathways known to impair insulin action.

MeSH Terms
Adult Diacylglycerol O-Acyltransferase/metabolism Exercise/physiology Fatty Acids/blood,metabolism Female Glycerol-3-Phosphate O-Acyltransferase/metabolism Humans Inflammation Mediators/metabolism Insulin Resistance/physiology Muscle, Skeletal/metabolism Oxidation-Reduction Stearoyl-CoA Desaturase/metabolism Triglycerides/biosynthesis
Chemicals
Fatty Acids Inflammation Mediators Triglycerides Stearoyl-CoA Desaturase Glycerol-3-Phosphate O-Acyltransferase Diacylglycerol O-Acyltransferase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Schenk Simon
Substrate Metabolism Laboratory, Division of Kinesiology, University of Michigan, Ann Arbor, Michigan 48109-2214, USA.
Horowitz Jeffrey F
References (54)
54 references, click to expand
  1. Palmitate-induced apoptosis can occur through a ceramide-independent pathway.
    J Biol Chem. 2001 May 4;276(18):14890-5 PMID: 11278654
  2. Thiazolidinediones enhance skeletal muscle triacylglycerol synthesis while protecting against fatty acid-induced inflammation and insulin resistance.
    Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E485-93 PMID: 17003244
  3. Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects.
    Am J Physiol Regul Integr Comp Physiol. 2001 Sep;281(3):R760-9 PMID: 11506990
  4. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta.
    Science. 2001 Aug 31;293(5535):1673-7 PMID: 11533494
  5. Thiazolidinedione treatment prevents free fatty acid-induced insulin resistance in male wistar rats.
    Diabetes. 2001 Oct;50(10):2316-22 PMID: 11574414
  6. Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans.
    Diabetes. 2001 Nov;50(11):2579-84 PMID: 11679437
  7. Mitochondrial glycerol phosphate acyltransferase directs the incorporation of exogenous fatty acids into triacylglycerol.
    J Biol Chem. 2001 Nov 9;276(45):42205-12 PMID: 11546763
  8. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes.
    J Clin Endocrinol Metab. 2001 Dec;86(12):5755-61 PMID: 11739435
  9. Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes.
    J Clin Invest. 2002 Jan;109(1):141-9 PMID: 11781359
  10. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha.
    Diabetes. 2002 Jul;51(7):2005-11 PMID: 12086926
  11. Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle.
    Biochem Biophys Res Commun. 2002 Aug 16;296(2):350-4 PMID: 12163024
  12. Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training.
    Biochem Biophys Res Commun. 2002 Aug 16;296(2):395-400 PMID: 12163031
  13. Dissociation of AMPK activity and ACCbeta phosphorylation in human muscle during prolonged exercise.
    Biochem Biophys Res Commun. 2002 Nov 1;298(3):309-16 PMID: 12413941
  14. Prior exercise increases subsequent utilization of dietary fat.
    Med Sci Sports Exerc. 2002 Nov;34(11):1757-65 PMID: 12439080
  15. A central role for JNK in obesity and insulin resistance.
    Nature. 2002 Nov 21;420(6913):333-6 PMID: 12447443
  16. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle.
    J Biol Chem. 2002 Dec 27;277(52):50230-6 PMID: 12006582
  17. Regulation of 5'AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle.
    Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E813-22 PMID: 12488245
  18. Skeletal muscle fat and carbohydrate metabolism during recovery from glycogen-depleting exercise in humans.
    J Physiol. 2003 May 1;548(Pt 3):919-27 PMID: 12651914
  19. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.
    Nat Genet. 2003 Jul;34(3):267-73 PMID: 12808457
  20. Insulin signalling: effects of prior exercise.
    Acta Physiol Scand. 2003 Aug;178(4):321-8 PMID: 12864736
  21. Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes.
    Arch Biochem Biophys. 2003 Nov 15;419(2):101-9 PMID: 14592453
  22. Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling.
    J Biol Chem. 2003 Nov 28;278(48):48453-66 PMID: 14504291
  23. Overexpression of diacylglycerol acyltransferase-1 reduces phospholipid synthesis, proliferation, and invasiveness in simian virus 40-transformed human lung fibroblasts.
    J Biol Chem. 2003 Dec 26;278(52):52203-11 PMID: 14557275
  24. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.
    N Engl J Med. 2004 Feb 12;350(7):664-71 PMID: 14960743
  25. Adding fat calories to meals after exercise does not alter glucose tolerance.
    J Appl Physiol (1985). 2004 Jul;97(1):11-6 PMID: 14978010
  26. Calculation of substrate oxidation rates in vivo from gaseous exchange.
    J Appl Physiol Respir Environ Exerc Physiol. 1983 Aug;55(2):628-34 PMID: 6618956
  27. Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men.
    Diabetes. 1985 Oct;34(10):973-9 PMID: 3930321
  28. Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp.
    J Clin Invest. 1987 Mar;79(3):790-800 PMID: 3546379
  29. Modified protocols improve insulin sensitivity estimation using the minimal model.
    Am J Physiol. 1987 Dec;253(6 Pt 1):E595-602 PMID: 2892414
  30. Prolonged increase in insulin-stimulated glucose transport in muscle after exercise.
    Am J Physiol. 1989 Apr;256(4 Pt 1):E494-9 PMID: 2650561
  31. Effect of exercise on insulin action in human skeletal muscle.
    J Appl Physiol (1985). 1989 Feb;66(2):876-85 PMID: 2496078
  32. A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.
    Diabetes. 1994 Sep;43(9):1114-21 PMID: 8070611
  33. Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed and skeletal muscle.
    J Clin Invest. 1996 Jul 1;98(1):125-35 PMID: 8690783
  34. Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects.
    N Engl J Med. 1996 Oct 31;335(18):1357-62 PMID: 8857019
  35. Identification of glycerol-3-phosphate acyltransferase as an adipocyte determination and differentiation factor 1- and sterol regulatory element-binding protein-responsive gene.
    J Biol Chem. 1997 Mar 14;272(11):7298-305 PMID: 9054427
  36. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat.
    Diabetes. 1997 Oct;46(10):1579-85 PMID: 9313753
  37. Role of glycogen-lowering exercise in the change of fat oxidation in response to a high-fat diet.
    Am J Physiol. 1997 Sep;273(3 Pt 1):E623-9 PMID: 9316454
  38. Diet-induced muscle insulin resistance in rats is ameliorated by acute dietary lipid withdrawal or a single bout of exercise: parallel relationship between insulin stimulation of glucose uptake and suppression of long-chain fatty acyl-CoA.
    Diabetes. 1997 Dec;46(12):2022-8 PMID: 9392490
  39. Fat balance in obese subjects: role of glycogen stores.
    Am J Physiol. 1998 Jun;274(6 Pt 1):E1027-33 PMID: 9611152
  40. Nuclear sterol regulatory element-binding proteins activate genes responsible for the entire program of unsaturated fatty acid biosynthesis in transgenic mouse liver.
    J Biol Chem. 1998 Dec 25;273(52):35299-306 PMID: 9857071
  41. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity.
    J Clin Invest. 1999 Jan;103(2):253-9 PMID: 9916137
  42. Effect of short-term fasting on lipid kinetics in lean and obese women.
    Am J Physiol. 1999 Feb;276(2 Pt 1):E278-84 PMID: 9950787
  43. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.
    Diabetologia. 1999 Jan;42(1):113-6 PMID: 10027589
  44. Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.
    Diabetes. 1999 Sep;48(9):1836-41 PMID: 10480616
  45. DGAT1 overexpression in muscle by in vivo DNA electroporation increases intramyocellular lipid content.
    J Lipid Res. 2005 Feb;46(2):230-6 PMID: 15576838
  46. Postexercise insulin sensitivity is not impaired after an overnight lipid infusion.
    Am J Physiol Endocrinol Metab. 2005 Mar;288(3):E519-25 PMID: 15522993
  47. Increased p85/55/50 expression and decreased phosphotidylinositol 3-kinase activity in insulin-resistant human skeletal muscle.
    Diabetes. 2005 Aug;54(8):2351-9 PMID: 16046301
  48. Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.
    Diabetes. 2006 Mar;55(3):760-7 PMID: 16505240
  49. Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites.
    J Appl Physiol (1985). 2006 May;100(5):1467-74 PMID: 16357064
  50. Ciliary neurotrophic factor prevents acute lipid-induced insulin resistance by attenuating ceramide accumulation and phosphorylation of c-Jun N-terminal kinase in peripheral tissues.
    Endocrinology. 2006 May;147(5):2077-85 PMID: 16396984
  51. Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle.
    Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E90-8 PMID: 16449296
  52. Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro.
    Diabetologia. 2006 Dec;49(12):3027-37 PMID: 17033839
  53. Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation.
    J Physiol. 2006 Dec 15;577(Pt 3):997-1007 PMID: 17008371
  54. Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects.
    Diabetes. 2001 Jul;50(7):1612-7 PMID: 11423483
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI30566
Published
2007-06-00
Epub
2007-00-17
Pages
1690-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1866251
Subset
IM
Grants
NCRR NIH HHS · M01 RR000042 · United States
NIDDK NIH HHS · P60 DK020572 · United States
NIDDK NIH HHS · 5P60 DK20572 · United States
NCRR NIH HHS · M01-RR00042 · United States
External Links
PubMed source DOI: 10.1172/JCI30566 PMC Full Text View journal details
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