Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women

Abstract

OBJECTIVE: We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 µg/m2 min for 60 min).

SUBJECTS: Ten obese women from 40.5±3.4 y old were selected for this study. Their body weight was 96.4±5.7 kg and their BMI was 35.3±1.7 kg/m2. They received a 2.5–2.9 MJ/day formula diet for 28 days.

DESIGN: Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis.

RESULTS: The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80–100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment.

CONCLUSION: The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol- and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Lafontan M, Berlan M . Fat cell adrenergic receptors and the control of white and brown fat cell function J Lipid Res 1993 34: 1057–1091.

    CAS  PubMed  Google Scholar 

  2. Dax E, Partilla JS, Gregerman RJ . Increased sensitivity to epinephrine-stimulated lipolysis during starvation: higher coupling of the adenylate cyclase complex Biochem Biophy Res Commun 1981 101: 1186–1192.

    Article  CAS  Google Scholar 

  3. Berlan M, Dang-Tran L, Lafontan M, Denard Y . Influence of hypocaloric diet on alpha-adrenergic responsiveness of obese human subcutaneous adipocytes Int J Obes 1981 5: 145–153.

    CAS  PubMed  Google Scholar 

  4. Amer P, Engfeldt P, Nowak J . In vivo observation on the lipolytic effect of noradrenaline during therapeutic fasting J Clin Endocr Metab 1981 53: 1207–1212.

    Article  Google Scholar 

  5. Jensen MD, Haymond MW, Gerich JE, Cryer PE, Miles JM . Lipolysis during fasting: decreased suppression by insulin and increased stimulation by epinephrine J Clin Invest 1987 87: 207–213.

    Article  Google Scholar 

  6. Stich V, Harant I, De Glisezinski I, Crampes F, Berlan M, Kunesova M, Hainer V, Dauzats M, Riviere D, Garrigues M, Holm C, Lafontan M, Langin D . Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in obese female identical twins J Clin Endocr Metab 1997 82: 63–69.

    PubMed  Google Scholar 

  7. Sengenes C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J . Natriuretic peptides: a new lipolytic pathway in human adipocytes FASEB J 2000 14: 1345–1351.

    Article  CAS  Google Scholar 

  8. Galitzky J, Sengenes C, Thalamas C, Marques MA, Senard JM, Lafontan M, Berlan M . The lipid mobilizing effect of natriuretic peptides is unrelated to sympathetic nervous system activation or obesity in young men J Lipid Res 2001 42: 536–544.

    CAS  PubMed  Google Scholar 

  9. Wolfe RR, Peter EJ, Klein S, Holland OB, Rosenblatt J, Gary H . Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects Am J Physiol 1987 252: E189–E196.

    CAS  PubMed  Google Scholar 

  10. Reynisdottir S, Langin D, Carlström K, Holm C, Rössner S, Arner P . Effects of weight reduction on the regulation of lipolysis in adipocytes of women with upper-body obesity Clin Sci 1995 89: 421–429.

    Article  CAS  Google Scholar 

  11. Barbe P, Stich V, Galitzky J, Kunesova M, Hainer V, Lafontan M, Berlan M . In vivo increase in β-adrenergic lipolytic response in subcutaneous adipose tissue of obese subjects submitted to a hypocaloric diet J Clin Endocr Metab 1997 82: 63–69.

    CAS  PubMed  Google Scholar 

  12. Weidmann P, Gnädinger MP, Ziswiler HR, Shaw S, Bachmann C, Rascher W, Uehlinger DE, Hasler L, Reubi FC . Cardiovascular, endocrine and renal effects of atrial natriuretic peptide in essential hypertension J Hypertension 1986 4: S71–S83.

    Article  CAS  Google Scholar 

  13. Uehlinger DE, Weidmann P, Gnädinger MP, Hasler L, Bachmann C, Shaw S, Hellmüller B, Lang RE . Increase in circulating insulin induced by atrial natriuretic peptide in normal humans J Cardio-vasc Pharmac 1986 8: 1122–1129.

    Article  CAS  Google Scholar 

  14. Dessi-Fulgheri P, Sarzani R, Serenelli M, Tamburrini P, Spagnolo D, Giantomassi L, Espinosa E, Rappelli A . Low calorie diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives Hypertension 1999 33: 658–662.

    Article  CAS  Google Scholar 

  15. Stich V, De Glisezinski I, Crampes F, Hejnova J, Cottet-Emard JM, Galitzky J, Lafontan M, Riviere D, Berlan M . Activation of α2-adrenergic receptors impairs exercise-induced lipolysis in subcutaneous adipose tissue of obese subjects Am J Physiol 2000 279: R499–R504.

    CAS  Google Scholar 

  16. Bernst E, Gutman I . Determination of ethanol with alcohol dehydrogenase and NAD. In: Bergmeyer HU (ed). Methods of enzymatic analysis Vol 3: Springer: Weinheim 1974 pp 1499–1505.

    Google Scholar 

  17. Bradley DC, Kaslow HR . Radiometric assays for glycerol, glucose and glycogen Anal Biochem 1989 180: 11–16.

    Article  CAS  Google Scholar 

  18. Jansson P-A, Larsson A, Smith U, Lönnroth P . Glycerol production in subcutaneous adipose tissue of lean and obese humans J Clin Invest 1992 89: 1610–1617.

    Article  CAS  Google Scholar 

  19. Barbe P, Millet L, Galitzky J, Lafontan M, Berlan M . In situ assessment of the role of β1-, β2-, β3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue Br J Pharmac 1996 117: 907–913.

    Article  CAS  Google Scholar 

  20. Jansson P-A, Smith U, Lönnroth P . Interstitial glycerol concentration measured by microdialysis in two subcutaneous regions in humans Am J Physiol 1990 258: E918–E922.

    CAS  PubMed  Google Scholar 

  21. Frayn KN, Shadid S, Hamlani R, Humphreys SM, Clark ML, Fielding BA, Boland O, Coppack SW . Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition Am J Physiol 1994 266: E308–E317.

    CAS  PubMed  Google Scholar 

  22. Zapf J, Waldvogel M, Froesch ER . Increased sensitivity of rat adipose tissue to the lipolytic action of epinephrine during fasting and its reversal during refeeding FEBS Lett. 1977 72: 135–138.

    Article  Google Scholar 

  23. Kather H, Wieland E, Fisher B, Wirth A, Schlierf G . Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition Eur J Clin Invest 1985 15: 30–37.

    Article  CAS  Google Scholar 

  24. Crampes F, Marceron M, Beauville M, Rivière D, Garrigues M, Berlan M, Lafontan M . Platelet alpha2-adrenoceptors and adrenergic adipose tissue responsiveness after moderate hypocaloric diet in obese subjects Int J Obes 1989 13: 99–110.

    CAS  PubMed  Google Scholar 

  25. Kempen KPG, Saris WHM, Senden JMG, Menheere PP, Blaak EE, Baak MAV . Effects of energy restriction on acute adrenoceptor and metabolic response to exercise in obese subjects Am J Physiol 1994 267: E694–E701.

    CAS  PubMed  Google Scholar 

  26. Hickner RC, Rosdahl H, Borg I, Ungerstedt U, Jorfeldt L, Henriksson J . Ethanol may be used with the microdialysis technique to monitor blood flow changes in skeletal muscle: dialysate glucose concentration is blood-flow dependent Acta Physiol Scand 1991 143: 355–356.

    Article  CAS  Google Scholar 

  27. Enocksson S, Nordenström J, Bolinder J, Arner P . Influence of local bood flow on glycerol levels in human adipose tissue Int J Obes Relat Metab Disord 1995 19: 350–354.

    Google Scholar 

  28. Landau BR, Wahren J, Previs SF, Ekberg K, Chandramouli V, Brunengraber H . Glycerol production and utilization in humans: sites and quantitation Am J Physiol 1996 271: E1110–E1117.

    CAS  PubMed  Google Scholar 

  29. Bortz WM, Paul P, Haff AC, Holmes WL . Glycerol turnover and oxidation in man J Clin Invest 1972 51: 1537–1546.

    Article  CAS  Google Scholar 

  30. Kekwick A, Pawan GLS, Chalmers TM . Resistance to ketosis in obese subjects Lancet 1959 ii: 1157–1159.

    Article  Google Scholar 

  31. 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.

    Article  CAS  Google Scholar 

  32. Arner PE . Kriegholm E, Engfeldt P. In vivo interactions between beta-1 and beta-2 adrenoceptors regulate catechomlaine tachyphylaxia in human adipose tissue J Pharmac Exp Ther 1991 259: 317–322.

    CAS  Google Scholar 

  33. Di Biase G, Mattioli PL, Contaldo F, Mancini M . A very-low-calorie formula diet (Cambridge diet) for the treatment of diabetic/obese patients Int J Obes 1981 5: 319–324.

    Google Scholar 

  34. Atkinson RL, Kaiser DL . Effects of calorie restriction and weight loss on glucose and insulin levels in obese humans J Am Coll Nutr 1985 4: 411–419.

    Article  CAS  Google Scholar 

  35. Verspohl EJ, Ammon HP . Atrial natriuretic peptide (ANP) acts via specific binding sites on cGMP system of rat pancreatic islets without affecting insulin release Naunyn Schmied Arch Pharmac 1989 339: 348–353.

    Article  CAS  Google Scholar 

  36. Fehmann HC, Noll B, Goke R, Goke B, Trautmann ME, Arnold R . Atrial natriuretic factor has a weak insulinotropic action in the isolated perfused rat pancreas Res Exp Med 1990 190: 253–258.

    Article  CAS  Google Scholar 

  37. Sarzani R, Paci MV, Dessi-Fulgheri P, Espinosa E, Rappelli A . Comparative analysis of atrial natriuretic peptide receptor expression in rat tissues J Hypertens 1993 11(Suppl 5): S214–S216.

    CAS  Google Scholar 

  38. Sarzani R, Dessi-Fulgheri P, Paci MV, Espinsoa E, Rappelli A . Expression of natriuretic peptide receptor expression in human adipose and other tissues J Endocrinol Invest 1996 19: 581–585.

    Article  CAS  Google Scholar 

  39. Sarzani R, Paci MV, Zingaretti C, Pierleoni C, Cinti S, Cola G, Rappelli A . Fasting inhibits natriuretic peptide clearance receptor expression in rat adipose tissue J Hypertens 1995 13: 1241–1246.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to express their gratitude to M-T Canal for its contribution to the study. The study was financially supported by the Commission of the European Communities RDT Programme (FATLINK: dietary fat, body weight control, and links between obesity and cardiovascular disease), the Fondation pour la Recherche Médicale, the Direction Générale de la Coopération Internationale et du Développement (Programme d'Action Intégré Franco-Tchéque), and a grant from the Czech Republic (grant IGA 4674).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Berlan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sengenes, C., Stich, V., Berlan, M. et al. Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women. Int J Obes 26, 24–32 (2002). https://doi.org/10.1038/sj.ijo.0801845

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801845

Keywords

This article is cited by

Search

Quick links