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Erschienen in: Diabetologia 8/2003

01.08.2003 | Article

Lifestyle changes and lipid metabolism gene expression and protein content in skeletal muscle of subjects with impaired glucose tolerance

verfasst von: M. Mensink, E. E. Blaak, H. Vidal, T. W. A. de Bruin, J. F. C. Glatz, W. H. M. Saris

Erschienen in: Diabetologia | Ausgabe 8/2003

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Abstract

Aims/hypothesis

Skeletal muscle of pre-diabetic patients is characterised by a diminished capacity to handle fatty acids. A diminished content of several enzymes involved in fatty-acid transport and oxidation have been suggested to underlie these defects. The aim of this study was to investigate whether the combination of dietary advice, increased physical activity and weight loss improves lipid metabolic gene and protein expression in skeletal muscle of subjects with impaired glucose tolerance.

Methods

Before and after 1 year of a lifestyle-intervention programme, expression of several genes and proteins involved in lipid metabolism were measured in vastus lateralis muscle biopsies from subjects in the intervention (n=7) and control group (n=6).

Results

After 1 year the intervention group had an improved glycaemic control and reduced body fat compared to the control group. Significant differences were observed for acetyl CoA-carboxylase 2 and uncoupling protein 2 expression (ACC2: −16.8±12.4% vs +51.5±32.3% for the intervention and control group respectively; p<0.05) (UCP2: −26.9±10.3% vs +10.5±6.2% for the intervention and control group respectively; p<0.05). Change in 3-hydroxyacyl-CoA dehydrogenase protein content tended to be different between groups (+3.2±1.1 vs −0.9±1.9 U/mg.ww for the intervention and control group, p=0.07).

Conclusions/interpretation

Lifestyle changes leading to an improved glycaemic control and reduced adiposity, resulted in a down-regulation of ACC-2 and UCP2 expression and in an increase in HAD protein content, reflecting a better capacity to utilise fatty acids.
Literatur
1.
Zurück zum Zitat Kelley DE, Mandarino LJ (2000) Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49:677–683PubMed Kelley DE, Mandarino LJ (2000) Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49:677–683PubMed
2.
Zurück zum Zitat Kelley DE, Simoneau JA (1994) Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J Clin Invest 94:2349–2356PubMed Kelley DE, Simoneau JA (1994) Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J Clin Invest 94:2349–2356PubMed
3.
Zurück zum Zitat Blaak EE, Wagenmakers AJ, Glatz JF et al. (2000) Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle. Am J Physiol Endocrinol Metab 279:E146–E154PubMed Blaak EE, Wagenmakers AJ, Glatz JF et al. (2000) Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle. Am J Physiol Endocrinol Metab 279:E146–E154PubMed
4.
Zurück zum Zitat Mensink M, Blaak EE, Baak MA van, Wagenmakers AJ, Saris WH (2001) Plasma free fatty acid uptake and oxidation are already diminished in subjects at high risk for developing type 2 diabetes. Diabetes 50:2548–2554PubMed Mensink M, Blaak EE, Baak MA van, Wagenmakers AJ, Saris WH (2001) Plasma free fatty acid uptake and oxidation are already diminished in subjects at high risk for developing type 2 diabetes. Diabetes 50:2548–2554PubMed
5.
Zurück zum Zitat Falholt K, Jensen I, Lindkaer Jensen S et al. (1988) Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetic patients. Diabet Med 5:27–31PubMed Falholt K, Jensen I, Lindkaer Jensen S et al. (1988) Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetic patients. Diabet Med 5:27–31PubMed
6.
Zurück zum Zitat 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 86:5755–5761PubMed 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 86:5755–5761PubMed
7.
Zurück zum Zitat Pan DA, Lillioja S, Kriketos AD et al. (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46:983–988PubMed Pan DA, Lillioja S, Kriketos AD et al. (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46:983–988PubMed
8.
Zurück zum Zitat Perseghin G, Scifo P, De Cobelli F et al. (1999) Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 48:1600–1606PubMed Perseghin G, Scifo P, De Cobelli F et al. (1999) Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 48:1600–1606PubMed
9.
Zurück zum Zitat McGarry JD (2002) Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51:7–18PubMed McGarry JD (2002) Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51:7–18PubMed
10.
Zurück zum Zitat Simoneau JA, Veerkamp JH, Turcotte LP and Kelley DE (1999) Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEB J 13:2051–2060PubMed Simoneau JA, Veerkamp JH, Turcotte LP and Kelley DE (1999) Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEB J 13:2051–2060PubMed
11.
Zurück zum Zitat Ruderman NB, Saha AK, Vavvas D, Witters LA (1999) Malonyl-CoA, fuel sensing, and insulin resistance. Am J Physiol 276:E1–E18PubMed Ruderman NB, Saha AK, Vavvas D, Witters LA (1999) Malonyl-CoA, fuel sensing, and insulin resistance. Am J Physiol 276:E1–E18PubMed
12.
Zurück zum Zitat Simoneau JA, Kelley DE, Neverova M and Warden CH (1998) Overexpression of muscle uncoupling protein 2 content in human obesity associates with reduced skeletal muscle lipid utilization. FASEB J 12:1739–1745PubMed Simoneau JA, Kelley DE, Neverova M and Warden CH (1998) Overexpression of muscle uncoupling protein 2 content in human obesity associates with reduced skeletal muscle lipid utilization. FASEB J 12:1739–1745PubMed
13.
Zurück zum Zitat Schrauwen P, Schaart G, Saris WH et al. (2000) The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects. Diabetologia 43:1408–1416 Schrauwen P, Schaart G, Saris WH et al. (2000) The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects. Diabetologia 43:1408–1416
14.
Zurück zum Zitat Blaak EE, Wolffenbuttel BH, Saris WH, Pelsers MM, Wagenmakers AJ (2001) Weight reduction and the impaired plasma-derived free fatty acid oxidation in type 2 diabetic subjects. J Clin Endocrinol Metab 86:1638–1644PubMed Blaak EE, Wolffenbuttel BH, Saris WH, Pelsers MM, Wagenmakers AJ (2001) Weight reduction and the impaired plasma-derived free fatty acid oxidation in type 2 diabetic subjects. J Clin Endocrinol Metab 86:1638–1644PubMed
15.
Zurück zum Zitat Kiens B (1997) Effect of endurance training on fatty acid metabolism: local adaptations. Med Sci Sports Exerc 29:640–645PubMed Kiens B (1997) Effect of endurance training on fatty acid metabolism: local adaptations. Med Sci Sports Exerc 29:640–645PubMed
16.
Zurück zum Zitat Tunstall RJ, Mehan KA, Wadley GD et al. (2002) Exercise training increases lipid metabolism gene expression in human skeletal muscle. Am J Physiol Endocrinol Metab 283:E66–E72PubMed Tunstall RJ, Mehan KA, Wadley GD et al. (2002) Exercise training increases lipid metabolism gene expression in human skeletal muscle. Am J Physiol Endocrinol Metab 283:E66–E72PubMed
17.
Zurück zum Zitat Spina RJ, Chi MM, Hopkins MG, Nemeth PM, Lowry OH, Holloszy JO (1996) Mitochondrial enzymes increase in muscle in response to 7–10 days of cycle exercise. J Appl Physiol 80:2250–2254 Spina RJ, Chi MM, Hopkins MG, Nemeth PM, Lowry OH, Holloszy JO (1996) Mitochondrial enzymes increase in muscle in response to 7–10 days of cycle exercise. J Appl Physiol 80:2250–2254
18.
Zurück zum Zitat Schrauwen P, Van Aggel-Leijssen DP, Hul G et al. (2002) The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-coA carboxylase-2 expression. Diabetes 51:2220–2226PubMed Schrauwen P, Van Aggel-Leijssen DP, Hul G et al. (2002) The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-coA carboxylase-2 expression. Diabetes 51:2220–2226PubMed
19.
Zurück zum Zitat Clarke SD, Gasperikova D, Nelson C, Lapillonne A, Heird WC (2002) Fatty acid regulation of gene expression: a genomic explanation for the benefits of the mediterranean diet. Ann NY Acad Sci 967:283–298PubMed Clarke SD, Gasperikova D, Nelson C, Lapillonne A, Heird WC (2002) Fatty acid regulation of gene expression: a genomic explanation for the benefits of the mediterranean diet. Ann NY Acad Sci 967:283–298PubMed
20.
Zurück zum Zitat Tuomilehto J, Lindstrom J, Eriksson JG et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350 Tuomilehto J, Lindstrom J, Eriksson JG et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350
21.
Zurück zum Zitat Knowler WC, Barrett-Connor E, Fowler SE, et al. (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403CrossRefPubMed Knowler WC, Barrett-Connor E, Fowler SE, et al. (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403CrossRefPubMed
22.
Zurück zum Zitat Mensink M, Feskens EJ, Saris WH, De Bruin TW, Blaak EE (2003) Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year. Int J Obes Relat Metab Disord 27:377–384CrossRefPubMed Mensink M, Feskens EJ, Saris WH, De Bruin TW, Blaak EE (2003) Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year. Int J Obes Relat Metab Disord 27:377–384CrossRefPubMed
23.
Zurück zum Zitat Siri W (1956) The gross composition of the body. Adv Bio Med Physiol 4:239–280 Siri W (1956) The gross composition of the body. Adv Bio Med Physiol 4:239–280
24.
Zurück zum Zitat Bergstrom J, Hermansen L, Hultman E, Saltin B (1967) Diet, muscle glycogen and physical performance. Acta Physiol Scand 71:140–150PubMed Bergstrom J, Hermansen L, Hultman E, Saltin B (1967) Diet, muscle glycogen and physical performance. Acta Physiol Scand 71:140–150PubMed
25.
Zurück zum Zitat Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159PubMed Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159PubMed
26.
Zurück zum Zitat Auboeuf D, Vidal H (1997) The use of the reverse transcription-competitive polymerase chain reaction to investigate the in vivo regulation of gene expression in small tissue samples. Anal Biochem 245:141–148CrossRefPubMed Auboeuf D, Vidal H (1997) The use of the reverse transcription-competitive polymerase chain reaction to investigate the in vivo regulation of gene expression in small tissue samples. Anal Biochem 245:141–148CrossRefPubMed
27.
Zurück zum Zitat Pelsers MM, Lutgerink JT, Nieuwenhoven FA et al. (1999) A sensitive immunoassay for rat fatty acid translocase (CD36) using phage antibodies selected on cell transfectants: abundant presence of fatty acid translocase/CD36 in cardiac and red skeletal muscle and up-regulation in diabetes. Biochem J 337:407–414CrossRefPubMed Pelsers MM, Lutgerink JT, Nieuwenhoven FA et al. (1999) A sensitive immunoassay for rat fatty acid translocase (CD36) using phage antibodies selected on cell transfectants: abundant presence of fatty acid translocase/CD36 in cardiac and red skeletal muscle and up-regulation in diabetes. Biochem J 337:407–414CrossRefPubMed
28.
Zurück zum Zitat Wodzig KW, Pelsers MM, van der Vusse GJ, Roos W, Glatz JF (1997) One-step enzyme-linked immunosorbent assay (ELISA) for plasma fatty acid-binding protein. Ann Clin Biochem 34:263–268PubMed Wodzig KW, Pelsers MM, van der Vusse GJ, Roos W, Glatz JF (1997) One-step enzyme-linked immunosorbent assay (ELISA) for plasma fatty acid-binding protein. Ann Clin Biochem 34:263–268PubMed
29.
Zurück zum Zitat Shepherd D, Garland PB (1969) The kinetic properties of citrate synthase from rat liver mitochondria. Biochem J 114:597–610PubMed Shepherd D, Garland PB (1969) The kinetic properties of citrate synthase from rat liver mitochondria. Biochem J 114:597–610PubMed
30.
Zurück zum Zitat Bergmeyer H (1974) 3-Hydroxyacyl CoA dehydrogenase. Lactate dehydrogenase. In: Bergmeyer H (ed.) Methods of enzymatic analysis, vol 1. Academic Press, New York Bergmeyer H (1974) 3-Hydroxyacyl CoA dehydrogenase. Lactate dehydrogenase. In: Bergmeyer H (ed.) Methods of enzymatic analysis, vol 1. Academic Press, New York
31.
Zurück zum Zitat Mensink M, Blaak E, Wagenmakers A, Saris W (2002) Fatty acid metabolism and impaired glucose tolerance: effect of a one-year lifestyle-intervention program (SLIM). Diabetes 51:A336 (Abstract) Mensink M, Blaak E, Wagenmakers A, Saris W (2002) Fatty acid metabolism and impaired glucose tolerance: effect of a one-year lifestyle-intervention program (SLIM). Diabetes 51:A336 (Abstract)
32.
Zurück zum Zitat Vidal H, Langin D, Andreelli F, Millet L, Larrouy D, Laville M (1999) Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects. Am J Physiol 277:E830–E837PubMed Vidal H, Langin D, Andreelli F, Millet L, Larrouy D, Laville M (1999) Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects. Am J Physiol 277:E830–E837PubMed
33.
Zurück zum Zitat Saleh MC, Wheeler MB, Chan CB (2002) Uncoupling protein-2: evidence for its function as a metabolic regulator. Diabetologia 45:174–187CrossRefPubMed Saleh MC, Wheeler MB, Chan CB (2002) Uncoupling protein-2: evidence for its function as a metabolic regulator. Diabetologia 45:174–187CrossRefPubMed
34.
Zurück zum Zitat Khalfallah Y, Fages S, Laville M, Langin D, Vidal H (2000) Regulation of uncoupling protein-2 and uncoupling protein-3 mRNA expression during lipid infusion in human skeletal muscle and subcutaneous adipose tissue. Diabetes 49:25–31PubMed Khalfallah Y, Fages S, Laville M, Langin D, Vidal H (2000) Regulation of uncoupling protein-2 and uncoupling protein-3 mRNA expression during lipid infusion in human skeletal muscle and subcutaneous adipose tissue. Diabetes 49:25–31PubMed
Metadaten
Titel
Lifestyle changes and lipid metabolism gene expression and protein content in skeletal muscle of subjects with impaired glucose tolerance
verfasst von
M. Mensink
E. E. Blaak
H. Vidal
T. W. A. de Bruin
J. F. C. Glatz
W. H. M. Saris
Publikationsdatum
01.08.2003
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 8/2003
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-003-1152-2

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