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.

  • Original Article
  • Published:

Impairment of nutritional regulation of adipose triglyceride lipase expression with age

International Journal of Obesity volume 32, pages 1193–1200 (2008)Cite this article

Abstract

Objective:

Fasting-induced lipolysis becomes less effective with age. We have studied whether nutritional regulation of adipose triglyceride lipase (ATGL)—with an important role in lipolysis in low energy states—is affected by age.

Design:

Wistar rats of different ages (from 1 to 13 months) were distributed in control and fasted groups (14 h-food deprivation). ATGL mRNA expression was measured in different adipose depots at different ages and in only one depot at 13 months by reverse transcription (RT)–PCR. ATGL protein levels were determined at 3 and 7 months (not at 13 months) by western blot. Nonesterified fatty acid (NEFA), insulin and leptin levels were assessed in serum by enzymatic assays.

Results:

ATGL expression was dependent on regional fat distribution, with higher levels in brown than in white adipose tissue depots; and was affected by age: ATGL mRNA was increased with age in the brown adipose tissue and was decreased in two of the studied white depots, the inguinal and retroperitoneal, not being affected in the epididymal and mesenteric. Age also affected ATGL nutritional regulation: fasting increased ATGL gene expression and protein levels in the different white adipose depots of the youngest rats (up to the age of 5 months), whereas there was no change in the oldest rats studied (7 and 13-months old). This was in agreement with the pattern of NEFA levels, which did not increase in serum of fasted rats in the oldest animals, whereas other homeostatic parameters, such as insulin and leptin, responded to fasting independently of age. ATGL expressed by brown adipose tissue was not affected by feeding conditions at any age.

Conclusion:

Nutritional regulation of ATGL expression in white adipose tissue is impaired with age, which could contribute to the increased difficulty for mobilizing lipids when animals are exposed to nutritional stress such as fasting.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Yu BP, Bertrand HA, Masoro EJ . Nutrition-aging influence of catecholamine-promoted lipolysis. Metabolism 1980; 29: 438–444.

    Article  CAS  Google Scholar 

  2. Roth GS, Tzankoff SP, Elahi D . Effects of age on control of lipolysis during fasting. J Gerontol 1981; 36: 391–397.

    Article  CAS  Google Scholar 

  3. Voss KH, Masoro EJ, Anderson W . Modulation of age-related loss of glucagon-promoted lipolysis by food restriction. Mech Ageing Dev 1982; 18: 135–149.

    Article  CAS  Google Scholar 

  4. Engfeldt P, Arner P . Lipolysis in human adipocytes, effects of cell size, age and of regional differences. Horm Metab Res Suppl 1988; 19: 26–29.

    CAS  PubMed  Google Scholar 

  5. Hoffman BB, Chang H, Farahbakhsh ZT, Reaven GM . Age-related decrement in hormone-stimulated lipolysis. Am J Physiol 1984; 247 (6 Part 1): E772–E777.

    CAS  PubMed  Google Scholar 

  6. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS . Regulation of lipolysis in adipocytes. Annu Rev Nutr 2007; 27: 79–101.

    Article  CAS  Google Scholar 

  7. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004; 306: 1383–1386.

    Article  CAS  Google Scholar 

  8. Villena JA, Roy S, Sarkadi-Nagy E, Kim KH, Sul HS . Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem 2004; 279: 47066–47075.

    Article  CAS  Google Scholar 

  9. Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW . Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem 2004; 279: 48968–48975.

    Article  CAS  Google Scholar 

  10. Smirnova E, Goldberg EB, Makarova KS, Lin L, Brown WJ, Jackson CL . ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells. EMBO Rep 2006; 7: 106–113.

    Article  CAS  Google Scholar 

  11. Kershaw EE, Schupp M, Guan HP, Gardner NP, Lazar MA, Flier JS . PPAR{gamma} regulates adipose triglyceride lipase in adipocytes in vitro and in vivo. Am J Physiol Endocrinol Metab 2007; 293: E1736–E1745.

    Article  CAS  Google Scholar 

  12. Kershaw EE, Hamm JK, Verhagen LA, Peroni O, Katic M, Flier JS . Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 2006; 55: 148–157.

    Article  CAS  Google Scholar 

  13. Lake AC, Sun Y, Li JL, Kim JE, Johnson JW, Li D et al. Expression, regulation, and triglyceride hydrolase activity of adiponutrin family members. J Lipid Res 2005; 46: 2477–2487.

    Article  CAS  Google Scholar 

  14. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006; 312: 734–737.

    Article  CAS  Google Scholar 

  15. Steinberg GR, Kemp BE, Watt MJ . Adipocyte triglyceride lipase expression in human obesity. Am J Physiol Endocrinol Metab 2007; 293: E958–E964.

    Article  CAS  Google Scholar 

  16. Kralisch S, Klein J, Lossner U, Bluher M, Paschke R, Stumvoll M et al. Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. Mol Cell Endocrinol 2005; 240: 43–49.

    Article  CAS  Google Scholar 

  17. Jocken JW, Langin D, Smit E, Saris WH, Valle C, Hul GB et al. Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Metab 2007; 92: 2292–2299.

    Article  CAS  Google Scholar 

  18. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  19. Caimari A, Oliver P, Palou A . Regulation of adiponutrin expression by feeding conditions in rats is altered in the obese state. Obesity (Silver Spring) 2007; 15: 591–599.

    Article  CAS  Google Scholar 

  20. Oliver P, Pico C, Palou A . Ontogenesis of leptin expression in different adipose tissue depots in the rat. Pflugers Arch 2001; 442: 383–390.

    Article  CAS  Google Scholar 

  21. Oliver P, Pico C, Palou A . Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and white adipose tissue depots during rat development. Cell Mol Life Sci 2001; 58: 470–476.

    Article  CAS  Google Scholar 

  22. Pond CM, Mattacks CA . The effects of noradrenaline and insulin on lipolysis in adipocytes isolated from nine different adipose depots of guinea-pigs. Int J Obes 1991; 15: 609–618.

    CAS  PubMed  Google Scholar 

  23. Sanchez J, Oliver P, Pico C, Palou A . Diurnal rhythms of leptin and ghrelin in the systemic circulation and in the gastric mucosa are related to food intake in rats. Pflugers Arch 2004; 448: 500–506.

    Article  CAS  Google Scholar 

  24. Oliver P, Ribot J, Rodriguez AM, Sanchez J, Pico C, Palou A . Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm. Pflugers Arch 2006; 452: 1–8.

    Article  Google Scholar 

  25. Palou A, Pico C, Bonet ML, Oliver P . The uncoupling protein, thermogenin. Int J Biochem Cell Biol 1998; 30: 7–11.

    Article  CAS  Google Scholar 

  26. Holm C . Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans 2003; 31 (Part 6): 1120–1124.

    Article  CAS  Google Scholar 

  27. Dax EM, Partilla JS, Gregerman RI . Mechanism of the age-related decrease of epinephrine-stimulated lipolysis in isolated rat adipocytes: beta-adrenergic receptor binding, adenylate cyclase activity, and cyclic AMP accumulation. J Lipid Res 1981; 22: 934–943.

    CAS  PubMed  Google Scholar 

  28. Lass A, Zimmermann R, Haemmerle G, Riederer M, Schoiswohl G, Schweiger M et al. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin–Dorfman Syndrome. Cell Metab 2006; 3: 309–319.

    Article  CAS  Google Scholar 

  29. Langin D, Dicker A, Tavernier G, Hoffstedt J, Mairal A, Ryden M et al. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 2005; 54: 3190–3197.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of the ISCIII. This work was supported by the Spanish Government (Ministerio de Educación y Ciencia, AGL2006-04887/ALI and AGL2004-07496/ALI). Our laboratory is a member of the European Research Network of Excellence NuGO (The European Nutrigenomics Organisation, EU contract: FOOD-CT-2004-506360 NUGO). AC is a recipient of a fellowship from the Government of the Balearic Islands.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain

    A Caimari, P Oliver & A Palou

Authors
  1. A Caimari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Oliver
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Palou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Palou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Caimari, A., Oliver, P. & Palou, A. Impairment of nutritional regulation of adipose triglyceride lipase expression with age. Int J Obes 32, 1193–1200 (2008). https://doi.org/10.1038/ijo.2008.69

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2008.69

Keywords

This article is cited by

Search

Advanced search

Quick links