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Published in: Diabetologia 8/2008

01-08-2008 | Article

Adipose tissue fatty acid metabolism in insulin-resistant men

Authors: A. S. T. Bickerton, R. Roberts, B. A. Fielding, H. Tornqvist, E. E. Blaak, A. J. M. Wagenmakers, M. Gilbert, S. M. Humphreys, F. Karpe, K. N. Frayn

Published in: Diabetologia | Issue 8/2008

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Abstract

Aims/hypothesis

Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulin-resistant overweight men (BMI 25–35 kg/m2).

Methods

In a cohort study we examined NEFA concentrations in men in the upper quartile of fasting insulin (n = 124) and in men with fasting insulin below the median (n = 159). In a metabolic study we examined NEFA metabolism in the fasting and postprandial states, in ten insulin-resistant men and ten controls.

Results

In the cohort study, fasting NEFA concentrations were not significantly different between the two groups (median values: insulin-resistant men, 410 µmol/l; controls, 445 µmol/l). However, triacylglycerol concentrations differed markedly (1.84 vs 1.18 mmol/l respectively, p < 0.001). In the metabolic study, arterial NEFA concentrations again did not differ between groups, whereas triacylglycerol concentrations were significantly higher in insulin-resistant men. Systemic NEFA production and the release of NEFA from subcutaneous adipose tissue, expressed per unit of fat mass, were both reduced in insulin-resistant men compared with controls (fasting values by 32%, p = 0.02, and 44%, p = 0.04 respectively). 3-Hydroxybutyrate concentrations, an index of hepatic fat oxidation and ketogenesis, were lower (p = 0.03).

Conclusions/interpretation

Adipose tissue NEFA output is not increased (per unit weight of tissue) in insulin resistance. On the contrary, it appears to be suppressed by high fasting insulin concentrations. Alterations in triacylglycerol metabolism are more marked than those in NEFA metabolism and are indicative of altered metabolic partitioning of fatty acids (decreased oxidation, increased esterification) in the liver.
Literature
3.
go back to reference Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846PubMedCrossRef Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846PubMedCrossRef
4.
go back to reference Unger RH (2003) Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 144:5159–5165PubMedCrossRef Unger RH (2003) Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 144:5159–5165PubMedCrossRef
5.
go back to reference Opie LH, Walfish PG (1963) Plasma free fatty acid concentrations in obesity. N Engl J Med 268:757–760PubMed Opie LH, Walfish PG (1963) Plasma free fatty acid concentrations in obesity. N Engl J Med 268:757–760PubMed
6.
go back to reference Groop LC, Bonadonna RC, Simonson DC, Petrides AS, Shank M, DeFronzo RA (1992) Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity. Am J Physiol 263:E79–E84PubMed Groop LC, Bonadonna RC, Simonson DC, Petrides AS, Shank M, DeFronzo RA (1992) Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity. Am J Physiol 263:E79–E84PubMed
7.
go back to reference Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588PubMed Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588PubMed
8.
go back to reference Guo Z, Hensrud DD, Johnson CM, Jensen MD (1999) Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes 48:1586–1592PubMedCrossRef Guo Z, Hensrud DD, Johnson CM, Jensen MD (1999) Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes 48:1586–1592PubMedCrossRef
9.
go back to reference Baldeweg SE, Golay A, Natali A, Balkau B, Del Prato S, Coppack SW (2000) Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans. European Group for the Study of Insulin Resistance (EGIR). Eur J Clin Invest 30:45–52PubMedCrossRef Baldeweg SE, Golay A, Natali A, Balkau B, Del Prato S, Coppack SW (2000) Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans. European Group for the Study of Insulin Resistance (EGIR). Eur J Clin Invest 30:45–52PubMedCrossRef
10.
go back to reference Coppack SW, Evans RD, Fisher RM et al (1992) Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal. Metabolism 41:264–272PubMedCrossRef Coppack SW, Evans RD, Fisher RM et al (1992) Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal. Metabolism 41:264–272PubMedCrossRef
11.
go back to reference Laws A, Hoen HM, Selby JV, Saad MF, Haffner SM, Howard BV (1997) Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Arterioscler Thromb Vasc Biol 17:64–71PubMed Laws A, Hoen HM, Selby JV, Saad MF, Haffner SM, Howard BV (1997) Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Arterioscler Thromb Vasc Biol 17:64–71PubMed
12.
go back to reference Groop LC, Bonadonna RC, DelPrato S et al (1989) Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J Clin Invest 84:205–213PubMedCrossRef Groop LC, Bonadonna RC, DelPrato S et al (1989) Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J Clin Invest 84:205–213PubMedCrossRef
13.
go back to reference Colberg SR, Simoneau JA, Thaete FL, Kelley DE (1995) Skeletal muscle utilization of free fatty acids in women with visceral obesity. J Clin Invest 95:1846–1853PubMedCrossRef Colberg SR, Simoneau JA, Thaete FL, Kelley DE (1995) Skeletal muscle utilization of free fatty acids in women with visceral obesity. J Clin Invest 95:1846–1853PubMedCrossRef
14.
go back to reference Mensink M, Blaak EE, van Baak MA, 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 50:2548–2554PubMedCrossRef Mensink M, Blaak EE, van Baak MA, 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 50:2548–2554PubMedCrossRef
15.
go back to reference 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
16.
go back to reference Risérus U, Sprecher D, Johnson T et al (2007) Activation of peroxisome proliferator-activated receptor (PPAR)δ promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men. Diabetes 57:332–339PubMedCrossRef Risérus U, Sprecher D, Johnson T et al (2007) Activation of peroxisome proliferator-activated receptor (PPAR)δ promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men. Diabetes 57:332–339PubMedCrossRef
17.
go back to reference Reeds DN, Stuart CA, Perez O, Klein S (2006) Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans. Metabolism 55:1658–1663PubMedCrossRef Reeds DN, Stuart CA, Perez O, Klein S (2006) Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans. Metabolism 55:1658–1663PubMedCrossRef
18.
go back to reference Bagdade JD, Porte D, Bierman EL (1969) The interaction of diabetes and obesity on the regulation of fat mobilization in man. Diabetes 18:759–772PubMed Bagdade JD, Porte D, Bierman EL (1969) The interaction of diabetes and obesity on the regulation of fat mobilization in man. Diabetes 18:759–772PubMed
19.
go back to reference Bickerton AS, Roberts R, Fielding BA et al (2007) Preferential uptake of dietary fatty acids in adipose tissue and muscle in the postprandial period. Diabetes 56:168–176PubMedCrossRef Bickerton AS, Roberts R, Fielding BA et al (2007) Preferential uptake of dietary fatty acids in adipose tissue and muscle in the postprandial period. Diabetes 56:168–176PubMedCrossRef
20.
go back to reference Tan GD, Neville MJ, Liverani E et al (2006) The in vivo effects of the Pro12Ala PPARγ2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank. Diabetologia 49:158–168PubMedCrossRef Tan GD, Neville MJ, Liverani E et al (2006) The in vivo effects of the Pro12Ala PPARγ2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank. Diabetologia 49:158–168PubMedCrossRef
21.
go back to reference Coppack SW, Fisher RM, Gibbons GF et al (1990) Postprandial substrate deposition in human forearm and adipose tissues in vivo. Clin Sci (Lond) 79:339–348 Coppack SW, Fisher RM, Gibbons GF et al (1990) Postprandial substrate deposition in human forearm and adipose tissues in vivo. Clin Sci (Lond) 79:339–348
22.
go back to reference Larsen OA, Lassen NA, Quaade F (1966) Blood flow through human adipose tissue determined with radioactive xenon. Acta Physiol Scand 66:337–345PubMedCrossRef Larsen OA, Lassen NA, Quaade F (1966) Blood flow through human adipose tissue determined with radioactive xenon. Acta Physiol Scand 66:337–345PubMedCrossRef
23.
go back to reference Greenfield ADM, Whitney RJ, Mowbray JF (1963) Methods for the investigation of peripheral blood flow. Br Med Bull 19:101–109PubMed Greenfield ADM, Whitney RJ, Mowbray JF (1963) Methods for the investigation of peripheral blood flow. Br Med Bull 19:101–109PubMed
24.
go back to reference Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef
25.
go back to reference Frayn KN, Coppack SW (2001) Assessment of white adipose tissue metabolism by measurement of arteriovenous differences. Methods Mol Biol 155:269–279PubMed Frayn KN, Coppack SW (2001) Assessment of white adipose tissue metabolism by measurement of arteriovenous differences. Methods Mol Biol 155:269–279PubMed
26.
go back to reference Wolfe RR (1992) Radioactive and stable isotope tracers in biomedicine. Wiley-Liss, New York Wolfe RR (1992) Radioactive and stable isotope tracers in biomedicine. Wiley-Liss, New York
27.
go back to reference Miles JM, Ellman MG, McClean KL, Jensen MD (1987) Validation of a new method for determination of free fatty acid turnover. Am J Physiol 252:E431–E438PubMed Miles JM, Ellman MG, McClean KL, Jensen MD (1987) Validation of a new method for determination of free fatty acid turnover. Am J Physiol 252:E431–E438PubMed
28.
go back to reference Clausen JO, Borch-Johnsen K, Ibsen H et al (1996) Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J Clin Invest 98:1195–1209PubMedCrossRef Clausen JO, Borch-Johnsen K, Ibsen H et al (1996) Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J Clin Invest 98:1195–1209PubMedCrossRef
29.
go back to reference Campbell PJ, Carlson MG, Nurjhan N (1994) Fat metabolism in human obesity. Am J Physiol 266:E600–E605PubMed Campbell PJ, Carlson MG, Nurjhan N (1994) Fat metabolism in human obesity. Am J Physiol 266:E600–E605PubMed
30.
go back to reference Arner P (1999) Catecholamine-induced lipolysis in obesity. Int J Obes 23(Suppl 1):10–13CrossRef Arner P (1999) Catecholamine-induced lipolysis in obesity. Int J Obes 23(Suppl 1):10–13CrossRef
31.
go back to reference Jocken JW, Langin D, Smit E et al (2007) Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Metab 92:2292–2299PubMedCrossRef Jocken JW, Langin D, Smit E et al (2007) Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Metab 92:2292–2299PubMedCrossRef
32.
go back to reference Lebovitz HE, Banerji MA (2005) Point: visceral adiposity is causally related to insulin resistance. Diabetes Care 28:2322–2325PubMedCrossRef Lebovitz HE, Banerji MA (2005) Point: visceral adiposity is causally related to insulin resistance. Diabetes Care 28:2322–2325PubMedCrossRef
33.
go back to reference Frayn KN (2000) Visceral fat and insulin resistance—causative or correlative? Brit J Nutr 83(Suppl 1):S71–S77PubMed Frayn KN (2000) Visceral fat and insulin resistance—causative or correlative? Brit J Nutr 83(Suppl 1):S71–S77PubMed
34.
go back to reference Miles JM, Jensen MD (2005) Counterpoint: visceral adiposity is not causally related to insulin resistance. Diabetes Care 28:2326–2328PubMedCrossRef Miles JM, Jensen MD (2005) Counterpoint: visceral adiposity is not causally related to insulin resistance. Diabetes Care 28:2326–2328PubMedCrossRef
35.
go back to reference Frayn KN, Coppack SW, Humphreys SM, Clark ML, Evans RD (1993) Periprandial regulation of lipid metabolism in insulin-treated diabetes mellitus. Metabolism 42:504–510PubMedCrossRef Frayn KN, Coppack SW, Humphreys SM, Clark ML, Evans RD (1993) Periprandial regulation of lipid metabolism in insulin-treated diabetes mellitus. Metabolism 42:504–510PubMedCrossRef
36.
go back to reference Olefsky JM, Farquhar JW, Reaven GM (1974) Reappraisal of the role of insulin in hypertriglyceridaemia. Am J Med 57:551–560PubMedCrossRef Olefsky JM, Farquhar JW, Reaven GM (1974) Reappraisal of the role of insulin in hypertriglyceridaemia. Am J Med 57:551–560PubMedCrossRef
37.
go back to reference Tobey TA, Greenfield M, Kraemer F, Reaven GM (1981) Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics, and plasma triglyceride levels in normotriglyceridemic man. Metabolism 30:165–171PubMedCrossRef Tobey TA, Greenfield M, Kraemer F, Reaven GM (1981) Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics, and plasma triglyceride levels in normotriglyceridemic man. Metabolism 30:165–171PubMedCrossRef
38.
go back to reference Hodson L, Bickerton AS, McQuaid SE et al (2007) The contribution of splanchnic fat to VLDL triglyceride is greater in insulin-resistant than insulin-sensitive men and women: studies in the postprandial state. Diabetes 56:2433–2441PubMedCrossRef Hodson L, Bickerton AS, McQuaid SE et al (2007) The contribution of splanchnic fat to VLDL triglyceride is greater in insulin-resistant than insulin-sensitive men and women: studies in the postprandial state. Diabetes 56:2433–2441PubMedCrossRef
39.
go back to reference Petersen KF, Dufour S, Savage DB et al (2007) The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci U S A 104:12587–12594PubMedCrossRef Petersen KF, Dufour S, Savage DB et al (2007) The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci U S A 104:12587–12594PubMedCrossRef
Metadata
Title
Adipose tissue fatty acid metabolism in insulin-resistant men
Authors
A. S. T. Bickerton
R. Roberts
B. A. Fielding
H. Tornqvist
E. E. Blaak
A. J. M. Wagenmakers
M. Gilbert
S. M. Humphreys
F. Karpe
K. N. Frayn
Publication date
01-08-2008
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-1040-x

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