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European Journal of Nutrition

, Volume 53, Issue 8, pp 1685–1697 | Cite as

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

  • Giorgio Biasiotto
  • Marialetizia Penza
  • Isabella Zanella
  • Moris Cadei
  • Luigi Caimi
  • Cristina Rossini
  • Annika I. Smeds
  • Diego Di Lorenzo
Original Contribution
  • 416 Downloads

Abstract

Purpose and background

The focus was directed to the study of two of the most lignan-rich food sources: sesame and flaxseeds. Recent epidemiological and experimental evidences suggesting that these foods may improve metabolic functions underlying metabolic syndrome (MetS).

Methods

To characterize the effect of these oilseeds on metabolic functions, we conducted an experimental study aimed at preventing adiposity and metabolic imbalance in a mouse model of high-fat diet (HFD)-induced MetS. Statistical analysis was performed by two-way analysis of variance test followed by post hoc Bonferroni analysis.

Results

We studied the effect of the oilseeds sesame and flaxseed on metabolic parameters in mice on a HFD. When the HFD was integrated with 20 % of sesame or flaxseed flours, the mice showed a decrease in body fat, already at day 15, from time 0. The size of the adipocytes was smaller in epididymal fat, liver steatosis was inhibited, and insulin sensitivity was higher in mice on the supplemented diets. The supplemented diets also resulted in a significant increase in the serum levels of the lignan metabolites enterodiol and enterolactone compared with the controls. The expression of genes associated with the inflammatory response, glucose metabolism, adipose metabolism and nuclear receptor were altered by the oilseed-supplemented diets. Some of the most abundant lignans in these oilseeds were studied in 3T3-L1 preadipocyte cells and were effective in inhibiting adipocyte differentiation at the minimal dose of 1 nM.

Conclusions

The consumption of sesame and flaxseed may be beneficial to decrease metabolic parameters that are generally altered in MetS.

Keywords

Oilseeds Lignans Metabolic syndrome Adipose deposition 3T3-L1 differentiation 

Notes

Acknowledgments

We thank Deborah Bordiga for histochemical analysis and Alessandro Bulla and Francesca Piazza for English writing and editing assistance. This work was supported in part by European Union Grants QLK4-CT-2002-02221 (EDERA) and LSHB-CT-2006-037168 (EXERA).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Milder IE, Feskens EJ, Arts IC, Bueno de Mesquita HB, Hollman PC, Kromhout D (2009) Intake of the plant lignans secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol in Dutch men and women. J Nutr 135:1202–1207Google Scholar
  2. 2.
    Ayres DC, Loike JD (1990) Lignans: chemical, biological and clinical properties. Cambridge University Press, Cambridge, MACrossRefGoogle Scholar
  3. 3.
    Smeds AI, Eklund PC, Sjöholm RE, Willför SM, Nishibe S, Deyama T, Holmbom BR (2007) Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts. J Agric Food Chem 55:1337–1346CrossRefGoogle Scholar
  4. 4.
    Webb AL, McCullough ML (2005) Dietary lignans: potential role in cancer prevention. Nutr Cancer 51:117–131CrossRefGoogle Scholar
  5. 5.
    Dixon RA (2004) Phytoestrogens. Annu Rev Plant Biol 55:225–261CrossRefGoogle Scholar
  6. 6.
    Mazur W, Wähälä K, Rasku S, Makkonen A, Hase T, Adlercreutz H (1999) Lignans and isoflavonoid polyphenols in tea and coffee. J Med Food 2:199–202CrossRefGoogle Scholar
  7. 7.
    Adlercreutz H (2007) Lignans and human health. Crit Rev Clin Lab Sci 44:483–525CrossRefGoogle Scholar
  8. 8.
    Fletcher RJ (2003) Food sources of phyto-oestrogens and their precursors in Europe. Br J Nutr 89(1):S39–S43CrossRefGoogle Scholar
  9. 9.
    Valsta LM, Kilkkinen A, Mazur W, Nurmi T, Lampi AM, Ovaskainen ML, Korhonen T, Adlercreutz H, Pietinen P (2003) Phyto-oestrogen database of foods and average intake in Finland. Br J Nutr 89:31–38CrossRefGoogle Scholar
  10. 10.
    Touillaud MS, Thiébaut AC, Fournier A, Niravong M, Boutron-Ruault MC, Clavel-Chapelon F (2007) Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J Natl Cancer Inst 99:475–486CrossRefGoogle Scholar
  11. 11.
    Moreno-Franco B, García-González Á, Montero-Bravo AM, Iglesias-Gutiérrez E, Úbeda N, Maroto-Núñez L, Adlercreutz H, Peñalvo JL (2011) Dietary alkylresorcinols and lignans in the Spanish diet: development of the alignia database. J Agric Food Chem 59:9827–9834CrossRefGoogle Scholar
  12. 12.
    Knust U, Spiegelhalder B, Strowitzki T, Owen RW (2006) Contribution of linseed intake to urine and serum enterolignan levels in German females: a randomised controlled intervention trial. Food Chem Toxicol 44:1057–1064CrossRefGoogle Scholar
  13. 13.
    Eeckhaut E, Struijs K, Possemiers S, Vincken JP, Keukeleire DD, Verstraete W (2008) Metabolism of the lignan macromolecule into enterolignans in the gastrointestinal lumen as determined in the simulator of the human intestinal microbial ecosystem. J Agric Food Chem 56:4806–4812CrossRefGoogle Scholar
  14. 14.
    Wang CZ, Ma XQ, Yang DH, Guo ZR, Liu GR, Zhao GX, Tang J, Zhang YN, Ma M, Cai SQ, Ku BS, Liu SL (2010) Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria. BMC Microbiol 16:115CrossRefGoogle Scholar
  15. 15.
    Suzuki R, Rylander-Rudqvist T, Saji S, Bergkvist L, Adlercreutz H, Wolk A (2008) Dietary lignans and postmenopausal breast cancer risk by oestrogen receptor status: a prospective cohort study of Swedish women. Br J Cancer 98:636–640CrossRefGoogle Scholar
  16. 16.
    Hallmans G, Zhang JX, Lundin E, Stattin P, Johansson A, Johansson I, Hultén K, Winkvist A, Aman P, Lenner P, Adlercreutz H (2003) Rye, lignans and human health. Proc Nutr Soc 62:193–199CrossRefGoogle Scholar
  17. 17.
    Bloedon LT, Balikai S, Chittams J, Cunnane SC, Berlin JA, Rader DJ, Szapary PO (2008) Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr 27:65–74CrossRefGoogle Scholar
  18. 18.
    Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi BH (2008) Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. J Womens Health (Larchmt) 17:355–366CrossRefGoogle Scholar
  19. 19.
    Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X (2009) Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 90:288–297CrossRefGoogle Scholar
  20. 20.
    Sturgeon SR, Volpe SL, Puleo E, Bertone-Johnson ER, Heersink J, Sabelawski S, Wahala K, Bigelow C, Kurzer MS (2010) Effect of flaxseed consumption on urinary levels of estrogen metabolites in postmenopausal women. Nutr Cancer 62:175–180CrossRefGoogle Scholar
  21. 21.
    Sturgeon SR, Heersink JL, Volpe SL, Bertone-Johnson ER, Puleo E, Stanczyk FZ, Sabelawski S, Wahala K, Kurzer MS, Bigelow C (2008) Effect of dietary flaxseed on serum levels of estrogens and androgens in postmenopausal women. Nutr Cancer 60:612–618CrossRefGoogle Scholar
  22. 22.
    Hallund J, Tetens I, Bügel S, Tholstrup T, Bruun JM (2008) The effect of a lignan complex isolated from flaxseed on inflammation markers in healthy postmenopausal women. Nutr Metab Cardiovasc Dis 18:497–502CrossRefGoogle Scholar
  23. 23.
    Prasad K (2010) Natural products in regression and slowing of progression of atherosclerosis. Curr Pharm Biotechnol 11:794–800CrossRefGoogle Scholar
  24. 24.
    Prasad K (2009) Flaxseed and cardiovascular health. J Cardiovasc Pharmacol 54:369–377CrossRefGoogle Scholar
  25. 25.
    Prasad K (2007) A study on regression of hypercholesterolemic atherosclerosis in rabbits by flax lignan complex. J Cardiovasc Pharmacol Ther 12:304–313CrossRefGoogle Scholar
  26. 26.
    Penumathsa SV, Koneru S, Thirunavukkarasu M, Zhan L, Prasad K, Maulik N (2007) Secoisolariciresinol diglucoside: relevance to angiogenesis and cardioprotection against ischemia-reperfusion injury. J Pharmacol Exp Ther 320:951–959CrossRefGoogle Scholar
  27. 27.
    Dodin S, Cunnane SC, Mâsse B, Lemay A, Jacques H, Asselin G, Tremblay-Mercier J, Marc I, Lamarche B, Légaré F, Forest JC (2008) Flaxseed on cardiovascular disease markers in healthy menopausal women: a randomized, double-blind, placebo-controlled trial. Nutrition 24:23–30CrossRefGoogle Scholar
  28. 28.
    Zhang S, Ho SC (2005) Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr 81:397–408Google Scholar
  29. 29.
    Wu WH, Kang YP, Wang NH, Jou HJ, Wang TA (2006) Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women. J Nutr 136:1270–1275Google Scholar
  30. 30.
    Carreau C, Flouriot G, Bennetau-Pelissero C, Potier M (2008) Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERalpha transcriptional activation in human breast cancer cells. J Steroid Biochem Mol Biol 110:176–185CrossRefGoogle Scholar
  31. 31.
    Penttinen P, Jaehrling J, Damdimopoulos AE, Inzunza J, Lemmen JG, van der Saag P, Pettersson K, Gauglitz G, Mäkelä S, Pongratz I (2007) Diet-derived polyphenol metabolite enterolactone is a tissue-specific estrogen receptor activator. Endocrinology 148:4875–4886CrossRefGoogle Scholar
  32. 32.
    Pan A, Sun J, Chen Y, Ye X, Li H, Yu Z, Wang Y, Gu W, Zhang X, Chen X, Demark-Wahnefried W, Liu Y, Lin X (2007) Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PLoS One 2:e1148CrossRefGoogle Scholar
  33. 33.
    Salas-Salvadó J, Fernández-Ballart J, Ros E, Martínez-González MA, Fitó M, Estruch R, Corella D, Fiol M, Gómez-Gracia E, Arós F, Flores G, Lapetra J, Lamuela-Raventós R, Ruiz-Gutiérrez V, Bulló M, Basora J, Covas MI (2008) Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one-year results of the PREDIMED randomized trial. Arch Intern Med 168:2449–2458CrossRefGoogle Scholar
  34. 34.
    Carlson JJ, Joey RD, Eisenmann C, Norman GJ, Ortiz KA, Young PC (2011) Dietary Fiber and nutrient density are inversely associated with the metabolic syndrome in US adolescents. J Am Diet Assoc 111:1688–1695CrossRefGoogle Scholar
  35. 35.
    Namiki M (2007) Nutraceutical functions of sesame: a review. Crit Rev Food Sci Nutr 47:651–673CrossRefGoogle Scholar
  36. 36.
    Muir AD, Westcott ND (2000) Quantitation of the lignan secoisolariciresinol diglucoside in baked goods containing flax seed or flax meal. J Agric Food Chem 48:4048–4052CrossRefGoogle Scholar
  37. 37.
    Grougnet R, Magiatis P, Mitaku S, Terzis A, Tillequin F, Skaltsounis AL (2006) New lignans from the perisperm of Sesamum indicum. J Agric Food Chem 54:7570–7574CrossRefGoogle Scholar
  38. 38.
    Milder IE, Arts IC, van de Putte B, Venema DP, Hollman PC (2005) Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol. Br J Nutr 93:393–402CrossRefGoogle Scholar
  39. 39.
    Smeds AI, Hakala K, Hurmerinta TT, Kortela L, Saarinen NM, Mäkelä SI (2006) Determination of plant and enterolignans in human serum by high-performance liquid chromatography with tandem mass spectrometric detection. J Pharm Biomed Anal 7:898–905CrossRefGoogle Scholar
  40. 40.
    Moazzami AA, Kamal-Eldin A (2006) Sesame seed is a rich source of dietary lignans. JAOCS 83:719–723Google Scholar
  41. 41.
    Papadakis EN, Lazarou D, Grougnet R, Magiatis P, Skaltsounis AL, Papadopoulou-Mourkidou E, Papadopoulos AI (2008) Effect of the form of the sesame-based diet on the absorption of lignans. Br J Nutr 100:1213–1219CrossRefGoogle Scholar
  42. 42.
    Wikul A, Damsud T, Kataoka K, Phuwapraisirisan P (2012) (+)-Pinoresinol is a putative hypoglycemic agent in defatted sesame (Sesamum indicum) seeds though inhibiting α-glucosidase. Bioorg Med Chem Lett 22:5215–5217CrossRefGoogle Scholar
  43. 43.
    Biswas A, Dhar P, Ghosh S (2010) Antihyperlipidemic effect of sesame (Sesamum indicum L.) protein isolate in rats fed a normal and high cholesterol diet. J Food Sci 75:H274–H279CrossRefGoogle Scholar
  44. 44.
    Jenkins DJ, Kendall CW, Vidgen E, Agarwal S, Rao AV, Rosenberg RS, Diamandis EP, Novokmet R, Mehling CC, Perera T, Griffin LC, Cunnane SC (1999) Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr 69:395–402Google Scholar
  45. 45.
    Babu US, Mitchell GV, Wiesenfeld P, Jenkins MY, Gowda H (2000) Nutritional and hematological impact of dietary flaxseed and defatted flaxseed meal in rats. Int J Food Sci Nutr 51:109–117CrossRefGoogle Scholar
  46. 46.
    Edel AL, Aliani M, Pierce GN (2013) Supported liquid extraction in the quantitation of plasma enterolignans using isotope dilution GC/MS with application to flaxseed consumption in healthy adults. J Chromatogr B Analyt Technol Biomed Life Sci 912:24–32CrossRefGoogle Scholar
  47. 47.
    Wu JH, Hodgson JM, Puddey IB, Belski R, Burke V, Croft KD (2009) Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women. Nutr Metab Cardiovasc Dis 19:774–780CrossRefGoogle Scholar
  48. 48.
    Kallio P, Tolppanen AM, Kolehmainen M, Poutanen K, Lindström J, Tuomilehto J, Kuulasmaa T, Kuusisto J, Pulkkinen L, Uusitupa M (2009) Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin. Int J Obes (Lond) 33:80–88CrossRefGoogle Scholar
  49. 49.
    Ning Y, Schuller AG, Bradshaw S, Rotwein P, Ludwig T, Frystyk J, Pintar JE (2006) Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5. Mol Endocrinol 2:2173–2186CrossRefGoogle Scholar
  50. 50.
    Gleason CE, Ning Y, Cominski TP, Gupta R, Kaestner KH, Pintar JE, Birnbaum MJ (2010) Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth. Mol Endocrinol 24:178–192CrossRefGoogle Scholar
  51. 51.
    Di Cola G, Cool MH, Accili D (1997) Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors. J Clin Invest 99:2538–2544CrossRefGoogle Scholar
  52. 52.
    Ramachandrappa S, Farooqi IS (2011) Genetic approaches to understanding human obesity. J Clin Invest 121:2080–2086CrossRefGoogle Scholar
  53. 53.
    McCullough RS, Edel AL, Bassett CM, Lavallée RK, Dibrov E, Blackwood DP, Ander BP, Pierce GN (2011) The alpha linolenic acid content of flaxseed is associated with an induction of adipose leptin expression. Lipids 6:1043–1052CrossRefGoogle Scholar
  54. 54.
    Woting A, Clavel T, Loh G, Blaut M (2010) Bacterial transformation of dietary lignans in gnotobiotic rats. FEMS Microbiol Ecol 72:507–514CrossRefGoogle Scholar
  55. 55.
    Gustafsson JA (2006) Comments to the paper “tools to evaluate estrogenic potency of dietary phytoestrogens: a consensus paper from the EU Thematic Network “Phytohealth” (QLKI-2002-2453)”. Genes Nutr 1:159–160CrossRefGoogle Scholar
  56. 56.
    Fukumitsu S, Aida K, Ueno N, Ozawa S, Takahashi Y, Kobori M (2008) Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice. Br J Nutr 100:669–676CrossRefGoogle Scholar
  57. 57.
    Dip R, Lenz S, Antignac JP, Le Bizec B, Gmuender H, Naegeli H (2008) Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocr Relat Cancer 1:161–173CrossRefGoogle Scholar
  58. 58.
    Yang XW, Huang X, Ahmat M (2008) New neolignan from seed of Myristica fragrans. Zhongguo Zhong Yao Za Zhi 33:397–402Google Scholar
  59. 59.
    Filleur F, Pouget C, Allais DP, Kaouadji M, Chulia AJ (2002) Lignans and neolignans from Myristica argentea Warb. Nat Prod Lett 16:1–7CrossRefGoogle Scholar
  60. 60.
    Han KL, Choi JS, Lee JY, Song J, Joe MK, Jung MH, Hwang JK (2008) Therapeutic potential of peroxisome proliferators–activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetes. Diabetes 57:737–745CrossRefGoogle Scholar
  61. 61.
    Malini N, Rajesh H, Berwal P, Phukan S, Balaji VN (2008) Analysis of crystal structures of LXRbeta in relation to plasticity of the ligand-binding domain upon ligand binding. Chem Biol Drug Des 71:140–154CrossRefGoogle Scholar
  62. 62.
    Quaedackers ME, van den Brink CE, van der Saag PT, Tertoolen LG (2007) Direct interaction between estrogen receptor alpha and NF-kappaB in the nucleus of living cells. Mol Cell Endocrinol 273:42–50CrossRefGoogle Scholar
  63. 63.
    Jennewein C, Kuhn AM, Schmidt MV, Meilladec-Jullig V, von Knethen A, Gonzalez FJ, Brüne B (2008) Sumoylation of peroxisome proliferator-activated receptor gamma by apoptotic cells prevents lipopolysaccharide-induced NCoR removal from kappaB binding sites mediating transrepression of proinflammatory cytokines. J Immunol 181:5646–5652CrossRefGoogle Scholar
  64. 64.
    Chang L, Zhang Z, Li W, Dai J, Guan Y, Wang X (2007) Liver-X-receptor activator prevents homocysteine-induced production of IgG antibodies from murine B lymphocytes via the ROS-NF-kappaB pathway. Biochem Biophys Res Commun 357:772–778CrossRefGoogle Scholar
  65. 65.
    Penza M, Montani C, Romani A, Vignolini P, Pampaloni B, Tanini A, Brandi ML, Alonso-Magdalena P, Nadal A, Ottobrini L, Parolini O, Bignotti E, Calza S, Maggi A, Grigolato PG, Di Lorenzo D (2006) Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner. Endocrinology 147:5740–5751CrossRefGoogle Scholar
  66. 66.
    Montani C, Penza M, Jeremic M, Biasiotto G, La Sala G, De Felici M, Ciana P, Maggi A, Di Lorenzo D (2008) Genistein is an efficient estrogen in the whole-body throughout mouse development. Toxicol Sci 103:57–67CrossRefGoogle Scholar
  67. 67.
    Abete I, Goyenechea E, Zulet MA, Martínez JA (2011) Obesity and metabolic syndrome: potential benefit from specific nutritional components. Nutr Metab Cardiovasc Dis 21:B1–B15CrossRefGoogle Scholar
  68. 68.
    Onat A (2011) Metabolic syndrome: nature, therapeutic solutions and options. Expert Opin Pharmacother 12:1887–1900CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Giorgio Biasiotto
    • 1
    • 2
  • Marialetizia Penza
    • 1
  • Isabella Zanella
    • 1
    • 2
  • Moris Cadei
    • 3
  • Luigi Caimi
    • 1
    • 2
  • Cristina Rossini
    • 4
  • Annika I. Smeds
    • 5
  • Diego Di Lorenzo
    • 1
  1. 1.Biotechnology/3rd LaboratoryCivic Hospital of BresciaBresciaItaly
  2. 2.Department of Molecular and Translational MedicineUniversity of BresciaBresciaItaly
  3. 3.Human Pathology II, School of MedicineUniversity of BresciaBresciaItaly
  4. 4.Department of Pathology I, School of MedicineUniversity of BresciaBresciaItaly
  5. 5.Laboratory of Wood and Paper ChemistryÅbo Akademi UniversityTurkuFinland

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