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Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

Abstract

OBJECTIVE:

Oral treatment with oleoyl-estrone induces the loss of body fat and improvement of insulin resistance. Since cholesterol levels are deeply affected by oleoyl-estrone, we investigated here whether short-term treatment affected cholesterol turnover and overall metabolite changes.

DESIGN:

Wistar female rats received a single oral dose of 10 μmol/kg oleoyl-estrone in 0.2 ml of sunflower oil. Groups of animals were killed at timed intervals and blood samples were taken. In a second experiment series, rats had implanted carotid and jugular cannulas and were given a single gavage of oleoyl-estrone. These rats were used for the measurement of the cholesterol turnover rate.

MEASUREMENTS:

Body weight change and food intake: Glucose, total and HDL-cholesterol, triacylglycerols, 3-hydroxybutyrate, nonesterified fatty acids, insulin, HOMA score in the rats of the first series. Cholesterol: Cholesterol pool changes and cholesterol turnover rates in the rats of the second series.

RESULTS:

OE induced early effects, decreasing food intake, cholesterol and HDL-cholesterol levels, and increasing insulin sensitivity (HOMA score). OE also increased cholesteryl-ester turnover, and decreased circulating total cholesterol, especially esterified cholesterol pools.

CONCLUSIONS:

The role of early changes in insulin sensitivity induced by oral OE cannot explain per se the deep changes in cholesterol handling, essentially a consequence of accelerated lipoprotein turnover. However, the increase in cholesteryl-ester turnover observed with OE treatment may be, at least in part, a consequence of the decrease in insulin resistance. The compounded effect of increased insulin sensitivity and accelerated lipoprotein turnover may help explain the early and marked hypocholesterolaemic effects of OE.

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References

  1. Sanchis D, Balada F, Grasa MM, Virgili J, Peinado J, Monserrat C, Fernández-López JA, Remesar X, Alemany M . Oleoyl-estrone induces the loss of body fat in rats. Int J Obes Relat Metab Disord 1996; 20: 588–594.

    CAS  Google Scholar 

  2. Grasa MM, Cabot C, Esteve M, Yubero P, Masanés RM, Blay M, Vilà R, López-Martí J, Fernández-López JA, Remesar X, Alemany M . Daily oral oleoyl-estrone gavage induces a dose-dependent loss of fat in Wistar rats. Obes Res 2001; 9: 202–209.

    Article  CAS  Google Scholar 

  3. Blay M, Peinado-Onsurbe J, Grasa MM, Díaz-Silva M, Fernández-López JA, Remesar X, Alemany M . Effect of oral oleoyl-estrone treatment on plasma lipoproteins and tissue lipase and lipase activities of Zucker lean and obese female rats. Int J Obes Relat Metab Disord 2002; 26: 618–626.

    Article  CAS  Google Scholar 

  4. Sanchis D, Balada F, Picó C, Grasa MM, Virgili J, Farrerons C, Palou A, Fernández-López JA, Remesar X, Alemany M . Rats receiving the slimming agent oleoyl-estrone in liposomes (Merlin-2) decrease food intake but maintain thermogenesis. Arch Physiol Biochem 1997; 105: 663–672.

    Article  CAS  Google Scholar 

  5. Sanchis D, Adán C, Ardévol A, Grasa MM, Cabot C, Balada F, Vilà R, Estruch J, Puerta ML, Fernández-López JA, Remesar X, Alemany M . Short-term treatment with oleoyl-estrone in liposomes (Merlin-2) strongly reduces the expression of the ob gene in young rats. Biochem J 1997; 326: 357–3608.

    Article  CAS  Google Scholar 

  6. Adán C, Cabot C, Esteve M, Grasa MM, Masanés R, Vilà R, Estruch J, Fernández-López JA, Remesar X, Alemany M . Oleoyl-estrone treatment affects the ponderostat setting differently in lean and in obese Zucker rats. Int J Obes Relat Metab Disord 1999; 22: 366–373.

    Article  Google Scholar 

  7. Remesar X, Fernández-López JA, Blay MT, Savall P, Salas A, Díaz-Silva M, Esteve M, Grasa MM, Alemany M . Effect of oral oleoyl-estrone on adipose tissue composition in male rats. Int J Obes Relat Metab Disord 2002; 26: 1092–1102.

    Article  CAS  Google Scholar 

  8. Remesar X, Guijarro P, Torregrosa C, Grasa MM, López J, Fernández-López JA, Alemany M . Oral oleoyl-estrone induces the rapid loss of body fat in Zucker lean rats fed a hyperlipidic diet. Int J Obes Relat Metab Disord 2000; 24: 1405–1412.

    Article  CAS  Google Scholar 

  9. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Teacher DF, Turner RC . Homeostasis model assessment: insulin resistance and B cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  10. Bonora E, Saggiani F, Targher G, Zenere MB, Alberiche M, Monauni T, Bonadonna RC, Muggeo M . Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity. Diabetes Care 2000; 23: 57–63.

    Article  CAS  Google Scholar 

  11. Dell RB, Mott GE, Jackson EM, Ramakrishnan R, Carey KD, McGill HC, Goodman DWS . Whole body and tissue cholesterol turnover in the baboon. J Lipid Res 1985; 26: 327–337.

    CAS  PubMed  Google Scholar 

  12. Robins SJ, Fasulo JM, Collins MA, Patton GM . Cholesterol exchange and synthesis in the live rat. J Lipid Res 1985; 26: 1230–1240.

    CAS  PubMed  Google Scholar 

  13. Folch J, Lees M, Sloane-Stanley GH . A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 232: 497–509.

    Google Scholar 

  14. Touchstone JC . Thin layer chromatographic procedures for lipid separation. J Chromatogr B 1995; 671: 169–195.

    Article  CAS  Google Scholar 

  15. Hobbs JT . Total blood volume: its measurement and significance. Medical Monographs. The Radiochemical Centre: Amersham; 1987.

    Google Scholar 

  16. Ferreira LDMC, Pulawa LK, Jensen DR, Eckel RH . Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance. Diabetes 2001; 50: 1064–1068.

    Article  CAS  Google Scholar 

  17. Ruotolo G, Howard BV . Dyslipemia of the metabolic syndrome. Curr Cardiol Rep 2002; 4: 494–500.

    Article  Google Scholar 

  18. Pihlajamäki J, Gylling H, Miettinen TA, Laakso M . Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. J Lipid Res 2004; 45: 507–512.

    Article  Google Scholar 

  19. Couillard C, Lamarche B, Tchernof A, Prud'homme D, Tremblay A, Bouchard C, Moorjani S, Nadeau A, Lupien PJ, Després JP . Plasma high-density lipoprotein cholesterol but not apolipoprotein A-I is a good correlate of the visceral obesity–insulin resistance dyslipidemic syndrome. Metabolism 1996; 45: 882–888.

    Article  CAS  Google Scholar 

  20. Ohnishi H, Saitoh S, Takagi S, Ohata J, Isobe T, Kikuchi Y, Takeuchi H, Shimamoto K . Relationship between insulin-resistance and remnant-like particle cholesterol. Atherosclerosis 2002; 164: 167–170.

    Article  CAS  Google Scholar 

  21. Chan DC, Watts GF, Barrett PHR, O'Neill FH, Redgrave TG, Thompson GR . Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome. Clin Sci 2003; 104: 383–388.

    Article  CAS  Google Scholar 

  22. Panarotto D, Remillard P, Bouffard L, Maheux P . Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue-specific manner. Eur J Clin Invest 2002; 32: 84–92.

    Article  CAS  Google Scholar 

  23. Riemens SC, van Tol A, Scheek LM, Dullaart RPF . Plasma cholesteryl ester transfer and hepatic lipase activity are related to high-density lipoprotein cholesterol in association with insulin resistance in type 2 diabetic and non-diabetic subjects. Scand J Clin Lab Invest 2001; 61: 1–9.

    CAS  PubMed  Google Scholar 

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Acknowledgements

Funding by grants 01/1300 and 01/1309 from the Fondo de Investigaciones Sanitarias from the Government of Spain is gratefully acknowledged.

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Correspondence to M Alemany.

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Cabot, C., Salas, A., Ferrer-Lorente, R. et al. Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat. Int J Obes 29, 534–539 (2005). https://doi.org/10.1038/sj.ijo.0802898

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