Skip to main content
Log in

Nutritional regulation of adipose tissue lipoprotein lipase is blunted in insulin resistant rats

  • Research Article
  • Published:
Central European Journal of Biology

Abstract

Background

Hypertriglyceridemia is a common lipid abnormality accompanying insulin resistance. This study was designed to assess the contribution of dysregulation of adipose tissue lipoprotein lipase (LPL) activity to the hypertriglyceridemia in a rat model of insulin resistance.

Methodology

Hereditary hypertriglyceridemic (HHTg) rats were challenged for two weeks on a high sucrose diet and LPL activity, angptl-4 expression and FFA utilisation in vitro were determined in adipose tissue.

Results

Compared to control rats (Wistar), HHTg rats exhibited hyperinsulinemia, impaired fatty acid storage in adipose tissue and elevated LPL activity both in fasting and after refeeding. The expression of angiopoietin-like protein 4 (angptl4), a fastinginduced control protein for LPL activity, was not increased in adipose tissue of fasted HHTg rats as it was in the control rats.

Conclusion

We conclude that LPL remains in its active form to a higher extent in HHTg rat adipose tissue due to the low expression of angptl4 on fasting. This is a possible consequence of the hyperinsulinemia. In combination with the impaired storage of fatty acids as triglycerides in adipose tissue in HHTg rats, the inflexibility of angptl4 expression may contribute to the establishment of hypertriglyceridemia in the insulin-resistant animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Preiss-Landl K., Zimmermann R., Hammerle G., Zechner R., Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism, Curr. Opin. Lipidol., 2002, 13, 471–481

    Article  PubMed  CAS  Google Scholar 

  2. Hultin M., Savonen R., Olivecrona T., Chylomicron metabolism in rats: lipolysis, recirculation of triglyceride-derived fatty acids in plasma FFA, and fate of core lipids as analyzed by compartmental modelling, J. Lipid. Res., 1996, 37, 1022–1036

    PubMed  CAS  Google Scholar 

  3. Bickerton A.S., Roberts R., Fielding B.A., Hodson L., Blaak E.E., Wagenmakers A.J., et al., Preferential uptake of dietary Fatty acids in adipose tissue and muscle in the postprandial period, Diabetes, 2007, 56, 168–176

    Article  PubMed  CAS  Google Scholar 

  4. Sadur C.N., Eckel R.H., Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique, J. Clin. Invest., 1982, 69, 1119–1125

    Article  PubMed  CAS  Google Scholar 

  5. Ashby P., Robinson D.S., Effects of insulin, glucocorticoids and adrenaline on the activity of rat adipose-tissue lipoprotein lipids, Biochem. J., 1980, 188, 185–192

    PubMed  CAS  Google Scholar 

  6. Eckel R.H., Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases, N. Engl. J. Med., 1989, 320, 1060–1068

    Article  PubMed  CAS  Google Scholar 

  7. Boivin A., Montplaisir I., Deshaies Y., Postprandial modulation of lipoprotein lipase in rats with insulin resistance, Am. J. Physiol., 1994, 267, E620–E627

    PubMed  CAS  Google Scholar 

  8. Khamzina L., Veilleux A., Bergeron S., Marette A., Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance, Endocrinogy, 2005, 146, 1473–1481

    Article  CAS  Google Scholar 

  9. Ueno M., Carvalheira J.B., Tambascia R.C., Bezerra R.M., Amaral M.E., Carneiro E.M., et al, Regulation of insulin signalling by hyperinsulinaemia: role of IRS-1/2 serine phosphorylation and the mTOR/p70 S6K pathway, Diabetologia, 2005, 48, 506–518

    Article  PubMed  CAS  Google Scholar 

  10. Lynch C.J., Hutson S.M., Patson B.J., Vaval A., Vary T.C., Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats, Am. J. Physiol. Endocrinol. Metab., 2002, 283, E824–E835

    PubMed  CAS  Google Scholar 

  11. Mori H., Inoki K., Masutani K., Wakabayashi Y., Komai K., Nakagawa R., et al, The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential, Biochem. Biophys. Res. Commun., 2009, 384, 471–475

    Article  PubMed  CAS  Google Scholar 

  12. Zdychova J., Kazdova L., Pelikanova T., Lindsley J.N., Anderson S., Komers R., Renal activity of Akt kinase in obese Zucker rats, Exp. Biol. Med., 2008, 233, 1231–1241

    Article  CAS  Google Scholar 

  13. Bergo M., Olivecrona G., Olivecrona T., Diurnal rhythms and effects of fasting and refeeding on rat adipose tissue lipoprotein lipase, Am. J. Physiol., 1996, 271, E1092–E1097

    PubMed  CAS  Google Scholar 

  14. Bergo M., Olivecrona G., Olivecrona T., Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting, Biochem. J., 1996, 313, 893–898

    PubMed  Google Scholar 

  15. Bergo M., Wu G., Ruge T., Olivecrona T., Downregulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on, J. Biol. Chem., 2002, 277, 11927–11932

    Article  PubMed  CAS  Google Scholar 

  16. Mandard S., Zandbergen F., van Straten E., Wahli W., Kuipers F., Muller M., et al., The fastinginduced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity, J. Biol. Chem., 2006, 281, 934–944

    Article  PubMed  CAS  Google Scholar 

  17. Lichtenstein L., Berbee J.F., van Dijk S.J., van Dijk K.W., Bensadoun A., Kema I.P., et al., Angptl4 upregulates cholesterol synthesis in liver via inhibition of LPL- and HL-dependent hepatic cholesterol uptake, Arterioscler. Thromb. Vasc. Biol., 2007, 27, 2420–2427

    Article  PubMed  CAS  Google Scholar 

  18. Yau M.H., Wang Y., Lam K.S., Zhang J., Wu D., Xu A., A highly conserved motif within the NH2-terminal coiled-coil domain of angiopoietin-like protein 4 confers its inhibitory effects on lipoprotein lipase by disrupting the enzyme dimerization, J. Biol. Chem., 2009, 284, 11942–11952

    Article  PubMed  CAS  Google Scholar 

  19. Mattijssen F., Kersten S., Regulation of triglyceride metabolism by Angiopoietin-like proteins, Biochim. Biophys. Acta, 2011, DOI: 10.1016/j. bbalip.2011.10.010

  20. Kersten S., Mandard S., Tan N.S., Escher P., Metzger D., Chambon P., et al., Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene, J. Biol. Chem., 2000, 275, 28488–28493

    Article  PubMed  CAS  Google Scholar 

  21. Yoon J.C., Chickering T.W., Rosen E.D., Dussault B., Qin Y., Soukas A., et al., Peroxisome proliferatoractivated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation, Mol. Cell. Biol., 2000, 20, 5343–5349

    Article  PubMed  CAS  Google Scholar 

  22. Yamada T., Ozaki N., Kato Y., Miura Y., Oiso Y., Insulin downregulates angiopoietin-like protein 4 mRNA in 3T3-L1 adipocytes, Biochem. Biophys. Res. Commun., 2006, 347, 1138–1144

    Article  PubMed  CAS  Google Scholar 

  23. Ruge T., Sukonina V., Kroupa O., Makoveichuk E., Lundgren M., Svensson M.K., et al., Effects of hyperinsulinemia on lipoprotein lipase, angiopoietinlike protein 4, and glycosylphosphatidylinositolanchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus, Metabolism, 2011, DOI: 10.1016/j.metabol.2011.09.014

  24. Sukonina V., Lookene A., Olivecrona T., Olivecrona G., Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue, Proc. Natl. Acad. Sci. USA, 2006, 103, 17450–17455

    Article  PubMed  CAS  Google Scholar 

  25. Li C., Genetics and regulation of angiopoietin-like proteins 3 and 4, Curr. Opin. Lipidol., 2006, 17, 152–156

    Article  PubMed  CAS  Google Scholar 

  26. Vrana A., Kazdova L., The hereditary hypertriglyceridemic nonobese rat: an experimental model of human hypertriglyceridemia, Transplant. Proc., 1990, 22, 2579

    PubMed  CAS  Google Scholar 

  27. Pravenec M., Kazdova L., Cahova M., Landa V., Zidek V., Mlejnek P., et al., Fat-specific transgenic expression of resistin in the spontaneously hypertensive rat impairs fatty acid re-esterification, Int. J. Obes., 2006, 30, 1157–1159

    Article  CAS  Google Scholar 

  28. Bengtsson-Olivecrona G., Olivecrona T., Assay of lipoprotein lipase and hepatic lipase, In: Skinner R., Converse C. (Eds.) Lipoprotein analysis. A practical approach, Oxford University Press, Oxford, 1992

    Google Scholar 

  29. Belfrage P., Vaughan M., Simple liquid-liquid partition system for isolation of labeled oleic acid from mixtures with glycerides, J. Lipid. Res., 1969, 10, 341–344

    PubMed  CAS  Google Scholar 

  30. Cahova M., Vavrinkova H., Meschisvilli E., Markova I., Kazdova L., The impaired response of non-obese hereditary hypertriglyceridemic rats to glucose load is associated with low glucose storage in energy reserves, Exp. Clin. Endocrinol. Diabetes, 2004, 112, 549–555

    Article  PubMed  CAS  Google Scholar 

  31. Koster A., Chao Y.B., Mosior M., Ford A., Gonzalez-DeWhitt P.A., Hale J.E., et al., Transgenic angiopoietin-like (angptl)4 overexpression and targeted disruption of angptl4 and angptl3: regulation of triglyceride metabolism, Endocrinology, 2005, 146, 4943–4950

    Article  PubMed  CAS  Google Scholar 

  32. Bergo M., Olivecrona G., Olivecrona T., Regulation of adipose tissue lipoprotein lipase in young and old rats, Int. J. Obes. Relat. Metab. Disord., 1997, 21, 980–986

    Article  PubMed  CAS  Google Scholar 

  33. Simsolo R.B., Ong J.M., Saffari B., Kern P.A., Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue, J. Lipid. Res., 1992, 33, 89–95

    PubMed  CAS  Google Scholar 

  34. Taylor K.G., Galton D.J., Holdsworth G., Insulinindependent diabetes: a defect in the activity of lipoprotein lipase in adipose tissue, Diabetologia, 1979, 16, 313–317

    Article  PubMed  CAS  Google Scholar 

  35. Bengtsson G., Olivecrona T., Lipoprotein lipase. Mechanism of product inhibition., Eur. J. Biochem., 1980, 106, 557–562

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Monika Cahova.

About this article

Cite this article

Cahova, M., Papackova, Z., Palenickova, E. et al. Nutritional regulation of adipose tissue lipoprotein lipase is blunted in insulin resistant rats. cent.eur.j.biol. 7, 201–209 (2012). https://doi.org/10.2478/s11535-012-0002-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11535-012-0002-y

Keywords

Navigation