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The conjugated linoleic acid ester of estrone induces the mobilisation of fat in male Wistar rats

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Abstract

We investigated whether the substitution of the fatty acid moiety in oleoyl-estrone (OE) by conjugated linoleic acid, i.e. conjugated linoleoyl-estrone (cLE) may help improve the antiobesity effects of OE. Overweight (17% fat) male rats were treated for 10 days with oral OE or cLE (10 nmol/g per day) and compared with controls receiving only the oily vehicle. Rat weight and food intake were measured daily. After killing by decapitation, body composition and main plasma parameters were analysed. cLE induced marked decreases in body weight, energy intake, carcass energy and body lipid, whilst sparing protein; the effects were not significantly different from those obtained with OE. Energy expenditure was unchanged, but energy intake decreased to 46% (OE) or 55% (cLE) of controls; whole body energy decreased by 29% (OE) or 24% (cLE) in the 10-day period studied. Plasma composition showed almost identical decreases in glucose and cholesterol elicited by OE and cLE, with a more marked decrease in triacylglycerols by OE and no effect of either on NEFA. OE decreased leptin and insulin levels, but the effects of cLE were more marked on both, with similar decreases in adiponectin. It can be concluded that cLE is a new drug of the OE family; its overall effects on energy were akin to those of OE, albeit fractionally less effective at the single dose tested. However, this lower potency on lipid mobilisation does not affect other effects, such as powerful hypercholesterolemic effects or the modulation of adiponectin. And last, but not least, cLE seems to produce a more marked decrease in leptin and insulin than OE, which may reflect a coordinate action of the conjugated linoleic acid moiety and the “OE effect” on target tissues. If that were the case, cLE may constitute an improvement over OE in its action on insulin resistance.

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References

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

    Article  Google Scholar 

  • Aminot-Gilchrist DV, Anderson HGI (2004) Insulin resistance-associated cardiovascular disease: potential benefits of conjugated linoleic acid. Am J Clin Nutr 79:1159S–1163S

    PubMed  CAS  Google Scholar 

  • Balada F, Sanchis D, Grasa MM, Virgili J, Estruch J, Fernández-López JA, Remesar X, Alemany M (1998) Differential short-term distribution of estrone and oleoyl-estrone administered in liposomes to lean and obese Zucker rats. Obesity Res 6:34–39

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Borg W, Shackleton CHL, Pahuja SL, Hochberg RB (1995) Long-lived testosterone esters in the rat. Proc Nat Acad Sci USA 92:545–1549

    Article  Google Scholar 

  • Cabot C, Grasa MM, Estruch J, Fernández-López JA, Remesar X, Alemany M (1998) Zucker obese rats are insensitive to the CRH-increasing effect of oleoyl-estrone. Brain Res Bull 46:529–534

    Article  PubMed  CAS  Google Scholar 

  • Cabot C, Salas A, Ferrer-Lorente R, Savall P, Remesar X, Fernández-López JA, Esteve M, Alemany M (2005) Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat. Int J Obesity 29:534–539

    CAS  Google Scholar 

  • Cabot C, González-Martínez D, Fernández-López JA, Alemany M (2007) In the rat, estrone sulphate is the main serum metabolite of oral oleoyl-estrone. J Endocrinol Invest, in press

  • Cho HJ, Kim WK, Kim EJ, Jung KC, Park S, Lee HS, Tyner AL, Park JHY (2003) Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. Am J Physiol 284:G996–G1005

    CAS  Google Scholar 

  • Delmonte P, Roach JAG, Mossoba MM, Losi G, Yurawecz MP (2004) Synthesis, isolation, and GC analysis of all the 6,8- to 13,15-cis/trans conjugated linoleic acid isomers. Lipids 39:185–191

    PubMed  CAS  Google Scholar 

  • Desroches S, Chouinard PY, Galibois I, Corneau L, Delisle J, Lamarche B, Couture P, Bergeron N (2005) Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men. Am J Clin Nutr 82:309–319

    PubMed  CAS  Google Scholar 

  • Díaz-Silva M, Grasa MM, Blay M, Fernández-López JA, Remesar X, Alemany M (2004) Strain variability in Zucker rats affects their response to oral oleoyl-estrone. Diab Nutr Metab 17:315–322

    Google Scholar 

  • Esteve M, Savall P, Blay MT, Fernández-López JA, Remesar X, Alemany M (2005) Intestinal handling of an oral oleoyl-estrone gavage by the rat. Life Sci 69:763–777

    Article  PubMed  CAS  Google Scholar 

  • Ferrer-Lorente R, García-Peláez B, Gómez-Ollés S, Fernández-López JA, Remesar X, Alemany M (2005a) Effects of oral estrone on rat energy balance. Steroids 70:667–672

    Article  CAS  Google Scholar 

  • Ferrer-Lorente R, Cabot C, Fernández-López JA, Alemany M (2005b) Combined effects of oleoyl-estrone and a 3-adrenergic agonist (CL316,243) on lipid stores of diet-induced overweight male Wistar rats. Life Sci 77:2051–2058

    Article  CAS  Google Scholar 

  • Field FJ (1984) Intestinal cholesterol esterase: intracellular enzyme or contamination of cytosol by pancreatic enzymes? J Lipid Res 25:389–399

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Gillis MH, Duckett SK, Sackmann JR, Realini CE, Keisler DH, Pringle TD (2004) Effects of supplemental rumen-protected conjugated linoleic acid or linoleic acid on feedlot performance, carcass quality, and leptin concentrations in beef cattle. J Anim Sci 82:851–859

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Grasa MM, Díaz-Silva M, Fernández-López JA, Remesar X, Alemany M (2003) Oleoyl-estrone decreases rat plasma insulin, leptin and adiponectin, lowering muscle and BAT glucose uptake. Int J Obesity 27 (Suppl 1):S43 (abstract)

    Google Scholar 

  • Harle L, Basaria S, Dobs AS (2005) Nebido: a long-acting injectable testosterone for the treatment of male hypogonadism. Expert Op Pharmacother 6:1751–1759

    Article  CAS  Google Scholar 

  • Hargrave KM, Li CL, Meyer BJ, Kachman SD, Hartzell DL, della Fera MA, Miner JL, Baile CA (2002) Adipose depletion and apoptosis induced by trans-10, Cis-12 conjugated linoleic acid in mice. Obes Res 10:1284–1290

    Article  PubMed  CAS  Google Scholar 

  • Hochberg RB (2003) Biological esterification of steroids. Endocr Rev 19:331–348

    Article  Google Scholar 

  • Kishimoto Y (1973) Fatty acid esters of testosterone in rat brain: identification, distribution, and some properties of enzymes which synthesize and hydrolyze the esters. Arch Biochem Biophys 159:528–542

    Article  PubMed  CAS  Google Scholar 

  • Lampen A, Leifheit M, Voss J, Nau H (2005) Molecular and cellular effects of cis-9, trans-11-conjugated linoleic acid in enterocytes: effects on proliferation, differentiation, and gene expression. Biochim Biophys Acta 1735:30–40

    PubMed  CAS  Google Scholar 

  • Larner JM, Maclusky NJ, Hochberg RB (1985) The naturally occurring C17 fatty acid esters of estradiol are long-acting estrogens. J Steroid Biochem 22:407–413

    Article  PubMed  CAS  Google Scholar 

  • Lee KW, Lee HJ, Cho HY, Kim YJ (2005) Role of the conjugated linoleic acid in the prevention of cancer. Crit Rev Food Sci Nutr 45:135–144

    Article  PubMed  CAS  Google Scholar 

  • Mellon-Nussbaum SH, Ponticorvo L, Schatz L, Hochberg RB (1982) Estradiol fatty-acid esters. The isolation and identification of the lipoidal derivative of estradiol synthesized in the bovine uterus. J Biol Chem 257:5678–5684

    PubMed  CAS  Google Scholar 

  • Nagao K, Inoue N, Wang YM, Yanagita T (2003) Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa/fa) rats. Biochem Biophys Res Commun 310:562–566

    Article  PubMed  CAS  Google Scholar 

  • Oh DK, Hong GH, Lee Y, Min SG, Sin HS, Cho SK (2003) Production of conjugated linoleic acid by isolated Bifidobacterium strains. World J Microbiol Biotechnol 19:907–912

    Article  CAS  Google Scholar 

  • Ohashi A, Matsushita Y, Shibata H, Kimura K, Miyashita K, Saito M (2004) Conjugated linoleic acid deteriorates insulin resistance in obese/diabetic mice in association with decreased production of adiponectin and leptin. J Nutr Sci Vitaminol 50:416–421

    PubMed  CAS  Google Scholar 

  • Pariza MW, Park Y, Cook ME (1999) Conjugated linoleic acid and the control of cancer and obesity. Toxicol Sci 52:107–110

    PubMed  CAS  Google Scholar 

  • Poirier H, Rouault C, Clement L, Niot I, Monnot MC, Guerre-Millo M, Besnard P (2005) Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated with a decrease in leptin and adiponectin plasma levels and pancreatic beta cell hyperplasia in the mouse. Diabetologia 48:1059–1065

    Article  PubMed  CAS  Google Scholar 

  • Rahman SM, Wang YM, Han SY, Cha JY, Fukuda H, Yanagita T (2001) Effects of short-term administration of conjugated linoleic acid on lipid metabolism in white and brown adipose tissues of starved/refed Otsuka Long-Evans Tokushima fatty rats. Food Res Int 34:515–520

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Risérus U, Arner P, Brismar K, Vessby B (2002a) Treatment with dietary trans10cis12 conjugated linoleic causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 25:1516–1521

    Article  PubMed  Google Scholar 

  • Risérus U, Basu S, Jovinge S, Fredrikson GN, Ärnlöv J, Vessby B (2002b) Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein. A potential link to fatty acid-induced insulin resistance. Circulation 106:1925–1929

    Article  PubMed  Google Scholar 

  • Romero MM, Esteve M, Alemany M (2006) Combined effects of oral oleoyl-estrone and limited food intake on body composition of young overweight male rats. Int J Obesity 30:1149–1156

    Article  CAS  Google Scholar 

  • Salas A, Esteve M, Grasa MM, Remesar X (2005) Rats treated with oleoyl-estrone maintain glucidic homeostasis: comparisons with a pair-fed model. Br J Nutr 94:738–745

    Article  PubMed  CAS  Google Scholar 

  • Salas A, Remesar X, Esteve M (2007) Oleoyl-estrone treatment activates apoptotic mechanisms in white adipose tissue. Life Sci 80:293–298

    Article  PubMed  CAS  Google Scholar 

  • Sanchis D, Balada F, Grasa MM, Virgili J, Peinado J, Monserrat C, Fernández-López JA, Remesar X, Alemany M (1996) Oleoyl-estrone induces the loss of body fat in rats. Int J Obesity 20:588–594

    CAS  Google Scholar 

  • 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 (1997) Short-term treatment with oleoyl-estrone in liposomes (Merlin-2) strongly reduces the expression of the ob gene in young rats. Biochem J 326:357–360

    PubMed  CAS  Google Scholar 

  • Sanchis D, Balada F, Farrerons C, Virgili J, Grasa MM, Adán C, Esteve M, Cabot C, Ardévol A, Vilà R, Fernández-López JA, Remesar X, Alemany M (1998) Structural determinants of oleoyl-estrone slimming effects. Life Sci 62:1349–1359

    Article  PubMed  CAS  Google Scholar 

  • Sanders SR, Teachey MK, Ptock A, Kraemer K, Hasselwander O, Henriksen EJ, Baumgard LH (2004) Effects of specific conjugated linoleic acid isomers on growth characteristics in obese Zucker rats. Lipids 39:537–543

    Article  PubMed  CAS  Google Scholar 

  • Steinhart H, Rickert R, Winkler K (2003) Identification and analysis of conjugated linoleic acid isomers (CLA). Eur J Med Res 8:370–372

    PubMed  CAS  Google Scholar 

  • Virgili J, Casals I, Peinado-Onsurbe J, Esteve M, Julve J, Fernández-López JA, Remesar X, Alemany M (1999) Distribution of oleoyl-estrone in rat plasma lipoproteins. Horm Metabol Res 31:597–601

    Article  CAS  Google Scholar 

  • Wang YM, Jones PJH (2004) Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obesity 28:941–955

    Article  CAS  Google Scholar 

  • Wang YM, Nagao K, Inoue N, Ujino Y, Shimada Y, Nagao T, Iwata T, Kamegai T, Yamauchi-Sato Y, Yanagita T (2006) Isomer-specific anti-obese and hypolipidemic properties of conjugated linoleic acid in obese OLETF rats. Biosci Biotechnol Biochem 70:355–362

    Article  PubMed  CAS  Google Scholar 

  • Wargent E, Sennitt MV, Stocker C, Mayes AE, Brown L, O’Dowd J, Wang S, Einerhand AWC, Mohede I, Arch JRS, Cawthorne MA (2005) Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation. Lipids Health Dis 4:3

    Article  PubMed  CAS  Google Scholar 

  • Wilson TA, Nicolosi RJ, Saati A, Kotyla T, Kritchevsky D (2006) Conjugated linoleic acid isomers reduce blood cholesterol levels but not aortic cholesterol accumulation in hypercholesterolemic hamsters. Lipids 41:41–48

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki M, Miyamoto Y, Chujo H, Nishiyama K, Tachibana H, Yamada K (2005) Trans 10, cis12-conjugated linoleic acid induces mitochondria-related apoptosis and lysosomal destabilization in rat hepatoma cells. Biochim Biophys Acta 1735:176–184

    PubMed  CAS  Google Scholar 

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Acknowledgements

This study was funded by grants PI052179 of the “Fondo de Investigaciones Sanitarias”, and BFU2005-00524 of the “Plan Nacional de Investigación en Biología Fundamental”, both from the Government of Spain. Thanks are given to Manhattan Pharmaceuticals for their kind gift of cLE.

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Authors and Affiliations

  1. Department of Nutrition and Food Science, Faculty of Biology, University of Barcelona, Av. Diagonal, 645, 08028, Barcelona, Spain

    M. M. Romero, M. Esteve, J. A. Fernández-López & M. Alemany

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  1. M. M. Romero
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  2. M. Esteve
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  3. J. A. Fernández-López
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  4. M. Alemany
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Correspondence to M. Alemany.

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Romero, M.M., Esteve, M., Fernández-López, J.A. et al. The conjugated linoleic acid ester of estrone induces the mobilisation of fat in male Wistar rats. Naunyn-Schmied Arch Pharmacol 375, 283–290 (2007). https://doi.org/10.1007/s00210-007-0148-8

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