Horm Metab Res 2001; 33(12): 701-707
DOI: 10.1055/s-2001-19140
Original Basic
© Georg Thieme Verlag Stuttgart · New York

In Vitro and In Vivo Impairment of α2-Adrenergic Receptor-Dependent Antilipolysis by Fatty Acids in Human Adipose Tissue

S. Gesta 1 , J. Hejnova 2 , M. Berlan 1 3 , D. Daviaud 1 , F. Crampes 1 4 , V. Stich 2 , P. Valet 1 , J.-S. Saulnier-Blache 1
  • 1 INSERM U317, Rangueil Hospital, Paul Sabatier University, Toulouse, France
  • 2 Department of Sport Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic
  • 3 Department of Medical and Clinical Pharmacology, Purpan Faculty of Medicine, Toulouse, France
  • 4 Department of Adaptation to Exercise, Purpan Hospital, Toulouse, France
Further Information

Publication History

Publication Date:
18 December 2001 (online)

The aim of the present study was to study the influence of fatty acids on the adrenergic control of lipolysis both in vitro and in vivo. Human subcutaneous adipose tissue explants were cultured for 48 h in the presence of 100 µM bromopalmitate (BrPal), and lipolysis was measured in isolated adipocytes. In control conditions, β-AR-dependent activation of lipolysis by epinephrine was almost undetectable, and could be fully restored by pharmacological blockade of α2-AR-dependent antilipolysis. After BrPal treatment, epinephrine became fully lipolytic and was no longer influenced by α2-AR-blockade. Radioligand binding analysis revealed that BrPal treatment led to a significant reduction in the coupling of α2-AR to G proteins. In parallel, a chronic and significant increase in plasma fatty acids resulting from a 4-day high-fat diet (HFD) was accompanied by an impairment of the amplifying effect of the α2-AR antagonist phentolamine on exercise-induced lipolysis (measured in the subcutaneous adipose tissue with the use of a microdialysis probe) normally observed after a low-fat diet. In conclusion, in vitro and in vivo studies showed that fatty acids impair α2-AR-dependent antilipolysis.

References

  • 1 Arner P, Kriegholm E, Engfeldt P, Bolinder J. Adrenergic regulation of lipolysis in situ at rest and during exercise.  J Clin Invest. 1990;  85 893-898
  • 2 Barbe P, Millet L, Galitzky J, Lafontan M, Berlan M. In situ assessment of the role of the β1-, β2- and β3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue.  Br J Pharmacol. 1996;  117 907-913
  • 3 Barbe P, Stich V, Galitzky J, Kunesova M, Hainer V, Lafontan M, Berlan M. In vivo increase of β-adrenergic lipolytic response in subcutaneous adipose tissue of obese subjects submitted to hypocaloric diet.  J Clin Endocrinol Metab. 1997;  82 63-69
  • 4 Bastie C, Holst D, Gaillard D, Jehl-Pietri C, Grimaldi P. Expression of Peroxisome Proliferator-activated Receptor PPARδ promotes induction of PPARγ and adipocyte differentiation in 3T3C2 fibroblasts.  J Biol Chem. 1999;  274 21 920-21 925
  • 5 Bernt E, Gutman I. Determination of ethanol with alcohol dehydrogenase and NAD. In: Academic BHL (ed). Methods of Enzymatic Analysis 1974: 1499-1505
  • 6 Bradley D C, Kaslow H R. Radiometric assays for glycerol, glucose, and glycogen.  Anal Biochem. 1989;  180 11-16
  • 7 Castan I, Valet P, Quideau N, Voisin T, Ambid L, Laburthe M, Lafontan M, Carpene C. Antilipolytic effects of alpha-2-adrenergic agonists, neuropeptide Y, adenosine, and PGE1 in mammal adipocytes.  Am J Physiol. 1994;  266 R1141-R1147
  • 8 de Glisezinski I, Harant I, Crampes F, Trudeau F, Felez A, Cottet-Emard J-M, Rivière D, Garrigue M. Effect of carbohydrate ingestion on adipose tissue lipolysis during long-lasting exercise in trained men.  J Appl Physiol. 1998;  84 1627-1632
  • 9 Enoksson S, Nordenström J, Bolinder J, Arner P. Influence of local blood flow on glycerol levels in human adipose tissue.  Int J Obesity. 1995;  19 350-354
  • 10 Galitzky J, Lafontan M, Nordenström J, Arner P. Role of vascular alpha2-adrenoceptors in regulating lipid mobilization from human adipose tissue.  J Clin Invest. 1993;  91 1997-2003
  • 11 Galitzky J, Larrouy D, Berlan M, Lafontan M. New tools for human fat cell alpha2A-adrenoceptor characterization. Identification on membranes and on intact cells using the antagonist [3H]RX821002.  J Pharmacol Exp Ther. 1990;  252 312-319
  • 12 Grimaldi P A, Knobel S M, Whitesell R R, Abumrad N A. Induction of aP2 gene expression by nonmetabolized long-chain fatty acids.  Proc Natl Acad Sci USA. 1992;  89 10 930-10 934
  • 13 Jansson E, Hjemdahl P, Kaijser L. Diet induced changes in sympatho-adrenal activity during submaximal exercise in relation to substrate utilization in man.  Acta Physiol Scand. 1982;  114 171-178
  • 14 Jump D B, Clarke S D. Regulation of gene expression by dietary fat.  Annu Rev Nutr. 1999;  19 63-90
  • 15 Lafontan M, Berlan M. Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of β- and α2-adrenoceptor properties.  Eur J Clin Invest. 1985;  15 341-346
  • 16 Lafontan M, Berlan M. Fat cell α2-adrenoceptors: the regulation of fat cell function and lipolysis.  Endocrine Rev. 1995;  16 716-738
  • 17 Mc P herson. Analysis of radioligand binding experiments: a collection of computer programs for IBM PC.  J Pharmacol Methods. 1985;  14 213-228
  • 18 Paris S, Samuel D, Jacques Y, Gache C, Franchi A, Ailhaud G. The role of serum albumin in the uptake of fatty acids by cultures cardiac cells from chick embryo.  Eur J Biochem. 1978;  83 235-243
  • 19 Stich V, de Glisezinski I, Crampes F, Hejnova J, Cottet-Emard J-M, Galitzky J, Lafontan M, Rivière D, Berlan M. Activation of α2-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects.  Am J Physiol Regulatory Intergrative Comp Physiol. 2000;  279 R499-R504
  • 20 Stich V, de Glisezinski I, Crampes F, Suljkovicova H, Galitzky J, Rivière D, Hejnova J, Lafontan M, Berlan M. Activation of α2-adrenergic receptors by epinephrine during exercise in human adipose tissue.  Am J Physiol Regulatory Intergrative Comp Physiol. 1999;  277 R1076-R1083
  • 21 Viguerie-Bacands N, Saulnier-Blache J, Dandine M, Dauzats M, Daviaud D, Langin D. Increase in Uncoupling Protein-2 mRNA expression by BRL49653 and bromopalmitate in human adipocytes.  Biochem Biophys Res Com. 1999;  256 138-141
  • 22 Wickramasinghe N S, Jo H, McDonald J M, Hardy R W. Stearate inhibition of breast cancer cell proliferation. A mechanism involving epidermal growth factor receptor and G-proteins.  Am J Pathol. 1996;  148 987-995

Jean-Sebastien Saulnier-Blache

INSERM U317, CHU Ranguiel
Université de Paul Sabatier

31403 Toulouse Cédex 4
France


Phone: + 33 (5) 62 17 29 56

Fax: + 33 (5) 61 33 17 21

Email: saulnier@toulouse.inserm.fr