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Diabetologia

Erschienen in:

01.05.2011 | Article

Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide

verfasst von: J. J. Dubé, F. Amati, F. G. S. Toledo, M. Stefanovic-Racic, A. Rossi, P. Coen, B. H. Goodpaster

Erschienen in: Diabetologia | Ausgabe 5/2011

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Abstract

Aims/hypothesis

Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide.

Methods

Sixteen overweight to obese adults (BMI 30.6 ± 0.8; 67.2 ± 4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL (n = 8) or EX (n = 8). Insulin sensitivity was determined using hyperinsulinaemic–euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry.

Results

Insulin sensitivity was improved with DIWL (20.6 ± 4.7%) and EX (19.2 ± 12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly (p < 0.05) decreased with DIWL and increased with EX. There were decreases in DAG with DIWL (−12.4 ± 14.6%) and EX (−40.9 ± 12.0%). Ceramide decreased with EX (−33.7 ± 11.2%), but not with DIWL. Dihydroceramide was decreased with both interventions. Sphingosine was decreased only with EX. Changes in total DAG, total ceramides and other sphingolipids did not correlate with changes in glucose disposal. Stearoyl-coenzyme A desaturase 1 (SCD1) content was decreased with DIWL (−19.5 ± 8.5%, p < 0.05), but increased with EX (19.6 ± 7.4%, p < 0.05). Diacylglycerol acyltransferase 1 (DGAT1) was unchanged with the interventions.

Conclusions/interpretation

Diet-induced weight loss and exercise training both improved insulin resistance and decreased DAG, while only exercise decreased ceramides, despite the interventions having different effects on IMTG. These alterations may be mediated through differential changes in skeletal muscle capacity for oxidation and triacylglycerol synthesis.

Trial registration:

ClinicalTrials.gov NCT00766298

Funding:

ADA Clinical Research Award (B. H. Goodpaster), NIH R01 AG20128 (B. H. Goodpaster), Obesity and Nutrition Research (1P30DK46204) and Clinical and Translational Research Centers (UL1 RR024153)

Nur mit Berechtigung zugänglich

Kim SH, Reaven GM (2008) Isolated impaired fasting glucose and peripheral insulin sensitivity: not a simple relationship. Diab Care 31:347–352CrossRef

Muoio DM, Newgard CB (2006) Obesity-related derangements in metabolic regulation. Annu Rev Biochem 75:367–401PubMedCrossRef

Bastie CC, Hajri T, Drover VA, Grimaldi PA, Abumrad NA (2004) CD36 in myocytes channels fatty acids to a lipase-accessible triglyceride pool that is related to cell lipid and insulin responsiveness. Diabetes 53:2209–2216PubMedCrossRef

Hegarty BD, Conney GJ, Kraegen EW, Furler SM (2002) Increased efficiency of fatty acid uptake contributes to lipid accumulation in skeletal muscle of high fat-fed insulin-resistant rats. Diabetes 51:1477–1484PubMedCrossRef

Phillips DI, Caddy S, Ilic V et al (1996) Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. Metabolism 45:947–950PubMedCrossRef

Goodpaster BH, Theriault R, Watkins SC, Kelley DE (2000) Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism 49:467–472PubMedCrossRef

Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL (1999) Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 48:839–847PubMedCrossRef

Goodpaster BH, He J, Watkins S, Kelley DE (2001) Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 86:5755–5761PubMedCrossRef

Dube JJ, Amati F, Stefanovic-Racic M, Toledo FG, Sauers SE, Goodpaster BH (2008) Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete’s paradox revisited. Am J Physiol Endocrinol Metab 294:E882–E888PubMedCrossRef

10.

Pruchnic R, Katsiaras A, He J, Kelley DE, Winters C, Goodpaster BH (2004) Exercise training increases intramyocellular lipid and oxidative capacity in older adults. Am J Physiol Endocrinol Metab 287:E857–E862PubMedCrossRef

11.

van Loon LJ, Koopman R, Manders R, van der Weegen W, van Kranenburg GP, Keizer HA (2004) Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes. Am J Physiol Endocrinol Metab 287:E558–E565PubMedCrossRef

12.

Tarnopolsky MA, Rennie CD, Robertshaw HA, Fedak-Tarnopolsky SN, Devries MC, Hamadeh MJ (2007) Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am J Physiol Regul Integr Comp Physiol 292:R1271–R1278PubMedCrossRef

13.

Schenk S, Horowitz JF (2007) Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Invest 117:1690–1698PubMedCrossRef

14.

Peter A, Weigert C, Staiger H et al (2009) 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. Diabetes 58:1757–1765PubMedCrossRef

15.

Smith IJ, Huffman KM, Durheim MT, Duscha BD, Kraus WE (2009) Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise. Physiol Genomics 36:149–157PubMed

16.

Mayer-Davis EJ, D’Agostino R Jr, Karter AJ et al (1998) Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study. JAMA 279:669–674PubMedCrossRef

17.

Chavez JA, Knotts TA, Wang L et al (2003) A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem 278:10297–10303PubMedCrossRef

18.

Adams JM 2nd, Pratipanawatr T, Berria R et al (2004) Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 53:25–31PubMedCrossRef

19.

Yu C, Cline GW, Zhang D et al (2002) 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 277:50230–50236PubMedCrossRef

20.

Summers SA (2006) Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 45:42–72PubMedCrossRef

21.

Hoy AJ, Brandon AE, Turner N et al (2009) Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation. Am J Physiol Endocrinol Metab 297:E67–E75PubMedCrossRef

22.

Moro C, Galgani JE, Luu L et al (2009) Influence of gender, obesity, and muscle lipase activity on intramyocellular lipids in sedentary individuals. J Clin Endocrinol Metab 94:3440–3447PubMedCrossRef

23.

Coen PM, Dube JJ, Amati F et al (2010) Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes 59:80–88PubMedCrossRef

24.

Skovbro M, Baranowski M, Skov-Jensen C et al (2008) Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity. Diabetologia 51:1253–1260PubMedCrossRef

25.

Schmitz-Peiffer C, Craig DL, Biden TJ (1999) Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J Biol Chem 274:24202–24210PubMedCrossRef

26.

Bruce CR, Thrush AB, Mertz VA et al. (2006) Endurance training in obese humans improves glucose tolerance, mitochondrial fatty acid oxidation and alters muscle lipid content. Am J Physiol Endocrinol Metab 291:E99–E107

27.

Bielawski J, Szulc ZM, Hannun YA, Bielawska A (2006) Simultaneous quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography–tandem mass spectrometry. Methods 39:82–91PubMedCrossRef

28.

Straczkowski M, Kowalska I, Nikolajuk A et al (2004) Relationship between insulin sensitivity and sphingomyelin signaling pathway in human skeletal muscle. Diabetes 53:1215–1221PubMedCrossRef

29.

Itani SI, Rudderman NB, Schmieder F, Boden G (2002) Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C and IκB-α. Diabetes 51:2005–2011PubMedCrossRef

30.

Erion DM, Shulman GI (2010) Diacylglycerol-mediated insulin resistance. Nat Med 16:400–402PubMedCrossRef

31.

Carrasco S, Merida I (2007) Diacylglycerol, when simplicity becomes complex. Trends Biochem Sci 32:27–36PubMedCrossRef

32.

Bartke N, Hannun YA (2009) Bioactive sphingolipids: metabolism and function. J Lipid Res 50(Suppl):S91–S96PubMedCrossRef

33.

Smith ER, Merrill AH, Obeid LM, Hannun YA (2000) Effects of sphingosine and other sphingolipids on protein kinase C. Methods Enzymol 312:361–373PubMedCrossRef

34.

Biddinger SB, Almind K, Miyazaki M, Kokkotou E, Ntambi JM, Kahn CR (2005) Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome. Diabetes 54:1314–1323PubMedCrossRef

35.

Pinnamaneni SK, Southgate RJ, Febbraio MA, Watt MJ (2006) Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro. Diabetologia 49:3027–3037PubMedCrossRef

36.

Schmitt B, Fluck M, Decombaz J et al (2003) Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes. Physiol Genomics 15:148–157PubMed

37.

Alsted TJ, Nybo L, Schweiger M et al (2009) Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training. Am J Physiol Endocrinol Metab 296:E445–E453PubMedCrossRef

38.

Bouchard C, An P, Rice T et al (1999) Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. J Appl Physiol 87:1003–1008PubMed

39.

Ichi I, Nakahara K, Kiso K, Kojo S (2007) Effect of dietary cholesterol and high fat on ceramide concentration in rat tissues. Nutrition 23:570–574PubMedCrossRef

Titel: Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide
verfasst von: J. J. Dubé
F. Amati
F. G. S. Toledo
M. Stefanovic-Racic
A. Rossi
P. Coen
B. H. Goodpaster
Publikationsdatum: 01.05.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 5/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2065-0

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Abstract

Aims/hypothesis

Methods

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