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Published in: Diabetologia 2/2008

Open Access 01-02-2008 | Article

Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men

Authors: J. W. E. Jocken, G. H. Goossens, A. M. J. van Hees, K. N. Frayn, M. van Baak, J. Stegen, M. T. W. Pakbiers, W. H. M. Saris, E. E. Blaak

Published in: Diabetologia | Issue 2/2008

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Abstract

Aims/hypothesis

Obesity is characterised by increased triacylglycerol storage in adipose tissue. There is in vitro evidence for a blunted beta-adrenergically mediated lipolytic response in abdominal subcutaneous adipose tissue (SAT) of obese individuals and evidence for this at the whole-body level in vivo. We hypothesised that the beta-adrenergically mediated effect on lipolysis in abdominal SAT is also impaired in vivo in obese humans.

Methods

We investigated whole-body and abdominal SAT glycerol metabolism in vivo during 3 h and 6 h [2H5]glycerol infusions. Arterio–venous concentration differences were measured in 13 lean and ten obese men after an overnight fast and during intravenous infusion of the non-selective beta-adrenergic agonist isoprenaline [20 ng (kg fat free mass)−1 min−1].

Results

Lean and obese participants showed comparable fasting glycerol uptake by SAT (9.7 ± 3.4 vs 9.3 ± 2.5% of total release, p = 0.92). Furthermore, obese participants showed an increased whole-body beta-adrenergically mediated lipolytic response versus lean participants. However, their fasting lipolysis was blunted [glycerol rate of appearance: 7.3 ± 0.6 vs 13.1 ± 0.9 μmol (kg fat mass)−1 min−1, p < 0.01], as was the beta-adrenergically mediated lipolytic response per unit SAT [Δ total glycerol release: 140 ± 71 vs 394 ± 112 nmol (100 g tissue)−1 min−1, p < 0.05] compared with lean participants. Net triacylglycerol flux tended to increase in obese compared with lean participants during beta-adrenergic stimulation [Δ net triacylglycerol flux: 75 ± 32 vs 16 ± 11 nmol (100 g tissue)−1 min−1, p = 0.06].

Conclusions/interpretation

We demonstrated in vivo that beta-adrenergically mediated lipolytic response is impaired systematically and in abdominal SAT of obese versus lean men. This may be important in the development or maintenance of increased triacylglycerol stores and obesity.
Literature
1.
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
2.
go back to reference Horowitz JF, Klein S (2000) Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women. Am J Physiol Endocrinol Metab 278:E1144–E1152PubMed Horowitz JF, Klein S (2000) Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women. Am J Physiol Endocrinol Metab 278:E1144–E1152PubMed
3.
go back to reference Blaak EE, Van Baak MA, Kemerink GJ, Pakbiers MT, Heidendal GA, Saris WH (1994) beta-Adrenergic stimulation of energy expenditure and forearm skeletal muscle metabolism in lean and obese men. Am J Physiol 267:E306–E315PubMed Blaak EE, Van Baak MA, Kemerink GJ, Pakbiers MT, Heidendal GA, Saris WH (1994) beta-Adrenergic stimulation of energy expenditure and forearm skeletal muscle metabolism in lean and obese men. Am J Physiol 267:E306–E315PubMed
4.
go back to reference Blaak EE, Van Baak MA, Kemerink GJ, Pakbiers MT, Heidendal GA, Saris WH (1994) beta-Adrenergic stimulation of skeletal muscle metabolism in relation to weight reduction in obese men. Am J Physiol 267:E316–E322PubMed Blaak EE, Van Baak MA, Kemerink GJ, Pakbiers MT, Heidendal GA, Saris WH (1994) beta-Adrenergic stimulation of skeletal muscle metabolism in relation to weight reduction in obese men. Am J Physiol 267:E316–E322PubMed
5.
go back to reference Bougneres P, Stunff CL, Pecqueur C, Pinglier E, Adnot P, Ricquier D (1997) In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity. J Clin Invest 99:2568–2573PubMedCrossRef Bougneres P, Stunff CL, Pecqueur C, Pinglier E, Adnot P, Ricquier D (1997) In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity. J Clin Invest 99:2568–2573PubMedCrossRef
6.
go back to reference Enoksson S, Talbot M, Rife F, Tamborlane WV, Sherwin RS, Caprio S (2000) Impaired in vivo stimulation of lipolysis in adipose tissue by selective beta2-adrenergic agonist in obese adolescent girls. Diabetes 49:2149–2153PubMedCrossRef Enoksson S, Talbot M, Rife F, Tamborlane WV, Sherwin RS, Caprio S (2000) Impaired in vivo stimulation of lipolysis in adipose tissue by selective beta2-adrenergic agonist in obese adolescent girls. Diabetes 49:2149–2153PubMedCrossRef
7.
go back to reference Hellstrom L, Langin D, Reynisdottir S, Dauzats M, Arner P (1996) Adipocyte lipolysis in normal weight subjects with obesity among first-degree relatives. Diabetologia 39:921–928PubMedCrossRef Hellstrom L, Langin D, Reynisdottir S, Dauzats M, Arner P (1996) Adipocyte lipolysis in normal weight subjects with obesity among first-degree relatives. Diabetologia 39:921–928PubMedCrossRef
8.
go back to reference Reynisdottir S, Wahrenberg H, Carlstrom K, Rossner S, Arner P (1994) Catecholamine resistance in fat cells of women with upper-body obesity due to decreased expression of beta 2-adrenoceptors. Diabetologia 37:428–435PubMed Reynisdottir S, Wahrenberg H, Carlstrom K, Rossner S, Arner P (1994) Catecholamine resistance in fat cells of women with upper-body obesity due to decreased expression of beta 2-adrenoceptors. Diabetologia 37:428–435PubMed
9.
go back to reference Kurpad A, Khan K, Calder AG et al (1994) Effect of noradrenaline on glycerol turnover and lipolysis in the whole body and subcutaneous adipose tissue in humans in vivo. Clin Sci (Lond) 86:177–184 Kurpad A, Khan K, Calder AG et al (1994) Effect of noradrenaline on glycerol turnover and lipolysis in the whole body and subcutaneous adipose tissue in humans in vivo. Clin Sci (Lond) 86:177–184
10.
go back to reference Coppack SW, Persson M, Judd RL, Miles JM (1999) Glycerol and nonesterified fatty acid metabolism in human muscle and adipose tissue in vivo. Am J Physiol 276:E233–E240PubMed Coppack SW, Persson M, Judd RL, Miles JM (1999) Glycerol and nonesterified fatty acid metabolism in human muscle and adipose tissue in vivo. Am J Physiol 276:E233–E240PubMed
11.
go back to reference Goossens GH, Blaak EE, Saris WH, van Baak MA (2004) Angiotensin II-induced effects on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects. J Clin Endocrinol Metab 89:2690–2696PubMedCrossRef Goossens GH, Blaak EE, Saris WH, van Baak MA (2004) Angiotensin II-induced effects on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects. J Clin Endocrinol Metab 89:2690–2696PubMedCrossRef
12.
go back to reference Larsen OA, Lassen NA, Quaade F (1966) Blood flow through human adipose tissue determined with radioactive xenon. Acta Physiol Scand 66:337–345PubMed Larsen OA, Lassen NA, Quaade F (1966) Blood flow through human adipose tissue determined with radioactive xenon. Acta Physiol Scand 66:337–345PubMed
13.
go back to reference Goossens GH, Jocken JW, Blaak EE, Schiffers PM, Saris WH, van Baak MA (2007) Endocrine role of the renin–angiotensin system in human adipose tissue and muscle: effect of beta-adrenergic stimulation. Hypertension 49:542–547PubMedCrossRef Goossens GH, Jocken JW, Blaak EE, Schiffers PM, Saris WH, van Baak MA (2007) Endocrine role of the renin–angiotensin system in human adipose tissue and muscle: effect of beta-adrenergic stimulation. Hypertension 49:542–547PubMedCrossRef
14.
go back to reference Abumrad NN, Rabin D, Diamond MP, Lacy WW (1981) Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man. Metabolism 30:936–940PubMedCrossRef Abumrad NN, Rabin D, Diamond MP, Lacy WW (1981) Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man. Metabolism 30:936–940PubMedCrossRef
15.
go back to reference Frayn KN, Coppack SW, Humphreys SM, Whyte PL (1989) Metabolic characteristics of human adipose tissue in vivo. Clin Sci (Lond) 76:509–516 Frayn KN, Coppack SW, Humphreys SM, Whyte PL (1989) Metabolic characteristics of human adipose tissue in vivo. Clin Sci (Lond) 76:509–516
16.
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
17.
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
18.
go back to reference Tan GD, Debard C, Tiraby C et al (2003) A “futile cycle” induced by thiazolidinediones in human adipose tissue? Nat Med 9:811–812; author reply 812PubMedCrossRef Tan GD, Debard C, Tiraby C et al (2003) A “futile cycle” induced by thiazolidinediones in human adipose tissue? Nat Med 9:811–812; author reply 812PubMedCrossRef
19.
go back to reference Reynisdottir S, Ellerfeldt K, Wahrenberg H, Lithell H, Arner P (1994) Multiple lipolysis defects in the insulin resistance (metabolic) syndrome. J Clin Invest 93:2590–2599PubMed Reynisdottir S, Ellerfeldt K, Wahrenberg H, Lithell H, Arner P (1994) Multiple lipolysis defects in the insulin resistance (metabolic) syndrome. J Clin Invest 93:2590–2599PubMed
20.
go back to reference Large V, Reynisdottir S, Langin D et al (1999) Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res 40:2059–2066PubMed Large V, Reynisdottir S, Langin D et al (1999) Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res 40:2059–2066PubMed
21.
go back to reference Lofgren P, Hoffstedt J, Ryden M et al (2002) Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. J Clin Endocrinol Metab 87:764–771PubMedCrossRef Lofgren P, Hoffstedt J, Ryden M et al (2002) Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. J Clin Endocrinol Metab 87:764–771PubMedCrossRef
22.
go back to reference Schiffelers SL, Saris WH, Boomsma F, van Baak MA (2001) beta(1)- and beta(2)-Adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men. J Clin Endocrinol Metab 86:2191–2199PubMedCrossRef Schiffelers SL, Saris WH, Boomsma F, van Baak MA (2001) beta(1)- and beta(2)-Adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men. J Clin Endocrinol Metab 86:2191–2199PubMedCrossRef
23.
go back to reference Karpe F, Tan GD (2005) Adipose tissue function in the insulin-resistance syndrome. Biochem Soc Trans 33:1045–1048PubMedCrossRef Karpe F, Tan GD (2005) Adipose tissue function in the insulin-resistance syndrome. Biochem Soc Trans 33:1045–1048PubMedCrossRef
24.
go back to reference Borsheim E, Lonnroth P, Knardahl S, Jansson PA (2000) No difference in the lipolytic response to beta-adrenoceptor stimulation in situ but a delayed increase in adipose tissue blood flow in moderately obese compared with lean men in the postexercise period. Metabolism 49:579–587PubMedCrossRef Borsheim E, Lonnroth P, Knardahl S, Jansson PA (2000) No difference in the lipolytic response to beta-adrenoceptor stimulation in situ but a delayed increase in adipose tissue blood flow in moderately obese compared with lean men in the postexercise period. Metabolism 49:579–587PubMedCrossRef
25.
go back to reference Schiffelers SL, Akkermans JA, Saris WH, Blaak EE (2003) Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men. Int J Obes Relat Metab Disord 27:227–231PubMedCrossRef Schiffelers SL, Akkermans JA, Saris WH, Blaak EE (2003) Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men. Int J Obes Relat Metab Disord 27:227–231PubMedCrossRef
26.
go back to reference Sjostrand M, Gudbjornsdottir S, Holmang A, Strindberg L, Ekberg K, Lonnroth P (2002) Measurements of interstitial muscle glycerol in normal and insulin-resistant subjects. J Clin Endocrinol Metab 87:2206–2211PubMedCrossRef Sjostrand M, Gudbjornsdottir S, Holmang A, Strindberg L, Ekberg K, Lonnroth P (2002) Measurements of interstitial muscle glycerol in normal and insulin-resistant subjects. J Clin Endocrinol Metab 87:2206–2211PubMedCrossRef
27.
go back to reference Havel RJ, Kane JP, Balasse EO, Segel N, Basso LV (1970) Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans. J Clin Invest 49:2017–2035PubMedCrossRef Havel RJ, Kane JP, Balasse EO, Segel N, Basso LV (1970) Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans. J Clin Invest 49:2017–2035PubMedCrossRef
28.
go back to reference Bulow J, Simonsen L, Wiggins D et al (1999) Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose. J Lipid Res 40:2034–2043PubMed Bulow J, Simonsen L, Wiggins D et al (1999) Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose. J Lipid Res 40:2034–2043PubMed
29.
go back to reference Samra JS, Simpson EJ, Clark ML et al (1996) Effects of epinephrine infusion on adipose tissue: interactions between blood flow and lipid metabolism. Am J Physiol 271:E834–E839PubMed Samra JS, Simpson EJ, Clark ML et al (1996) Effects of epinephrine infusion on adipose tissue: interactions between blood flow and lipid metabolism. Am J Physiol 271:E834–E839PubMed
30.
go back to reference Yukht A, Davis RC, Ong JM, Ranganathan G, Kern PA (1995) Regulation of lipoprotein lipase translation by epinephrine in 3T3-L1 cells. Importance of the 3′ untranslated region. J Clin Invest 96:2438–2444PubMed Yukht A, Davis RC, Ong JM, Ranganathan G, Kern PA (1995) Regulation of lipoprotein lipase translation by epinephrine in 3T3-L1 cells. Importance of the 3′ untranslated region. J Clin Invest 96:2438–2444PubMed
31.
go back to reference Ong JM, Saffari B, Simsolo RB, Kern PA (1992) Epinephrine inhibits lipoprotein lipase gene expression in rat adipocytes through multiple steps in posttranscriptional processing. Mol Endocrinol 6:61–69PubMedCrossRef Ong JM, Saffari B, Simsolo RB, Kern PA (1992) Epinephrine inhibits lipoprotein lipase gene expression in rat adipocytes through multiple steps in posttranscriptional processing. Mol Endocrinol 6:61–69PubMedCrossRef
Metadata
Title
Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men
Authors
J. W. E. Jocken
G. H. Goossens
A. M. J. van Hees
K. N. Frayn
M. van Baak
J. Stegen
M. T. W. Pakbiers
W. H. M. Saris
E. E. Blaak
Publication date
01-02-2008
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 2/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0866-y

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