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.
Similar content being viewed by others
References
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 135:1202–1207
Ayres DC, Loike JD (1990) Lignans: chemical, biological and clinical properties. Cambridge University Press, Cambridge, MA
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 55:1337–1346
Webb AL, McCullough ML (2005) Dietary lignans: potential role in cancer prevention. Nutr Cancer 51:117–131
Dixon RA (2004) Phytoestrogens. Annu Rev Plant Biol 55:225–261
Mazur W, Wähälä K, Rasku S, Makkonen A, Hase T, Adlercreutz H (1999) Lignans and isoflavonoid polyphenols in tea and coffee. J Med Food 2:199–202
Adlercreutz H (2007) Lignans and human health. Crit Rev Clin Lab Sci 44:483–525
Fletcher RJ (2003) Food sources of phyto-oestrogens and their precursors in Europe. Br J Nutr 89(1):S39–S43
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 89:31–38
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 99:475–486
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 59:9827–9834
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 44:1057–1064
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 56:4806–4812
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 16:115
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 98:636–640
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 62:193–199
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 27:65–74
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) 17:355–366
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 90:288–297
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 62:175–180
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 60:612–618
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 18:497–502
Prasad K (2010) Natural products in regression and slowing of progression of atherosclerosis. Curr Pharm Biotechnol 11:794–800
Prasad K (2009) Flaxseed and cardiovascular health. J Cardiovasc Pharmacol 54:369–377
Prasad K (2007) A study on regression of hypercholesterolemic atherosclerosis in rabbits by flax lignan complex. J Cardiovasc Pharmacol Ther 12:304–313
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 320:951–959
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 24:23–30
Zhang S, Ho SC (2005) Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr 81:397–408
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 136:1270–1275
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 110:176–185
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 148:4875–4886
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:e1148
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 168:2449–2458
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 111:1688–1695
Namiki M (2007) Nutraceutical functions of sesame: a review. Crit Rev Food Sci Nutr 47:651–673
Muir AD, Westcott ND (2000) Quantitation of the lignan secoisolariciresinol diglucoside in baked goods containing flax seed or flax meal. J Agric Food Chem 48:4048–4052
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 54:7570–7574
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 93:393–402
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 7:898–905
Moazzami AA, Kamal-Eldin A (2006) Sesame seed is a rich source of dietary lignans. JAOCS 83:719–723
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 100:1213–1219
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 22:5215–5217
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–H279
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 69:395–402
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 51:109–117
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 912:24–32
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 19:774–780
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) 33:80–88
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 2:2173–2186
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 24:178–192
Di Cola G, Cool MH, Accili D (1997) Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors. J Clin Invest 99:2538–2544
Ramachandrappa S, Farooqi IS (2011) Genetic approaches to understanding human obesity. J Clin Invest 121:2080–2086
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 6:1043–1052
Woting A, Clavel T, Loh G, Blaut M (2010) Bacterial transformation of dietary lignans in gnotobiotic rats. FEMS Microbiol Ecol 72:507–514
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 1:159–160
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 100:669–676
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 1:161–173
Yang XW, Huang X, Ahmat M (2008) New neolignan from seed of Myristica fragrans. Zhongguo Zhong Yao Za Zhi 33:397–402
Filleur F, Pouget C, Allais DP, Kaouadji M, Chulia AJ (2002) Lignans and neolignans from Myristica argentea Warb. Nat Prod Lett 16:1–7
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 57:737–745
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 71:140–154
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 273:42–50
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 181:5646–5652
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 357:772–778
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 147:5740–5751
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 103:57–67
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–B15
Onat A (2011) Metabolic syndrome: nature, therapeutic solutions and options. Expert Opin Pharmacother 12:1887–1900
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Giorgio Biasiotto and Marialetizia Penza have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Biasiotto, G., Penza, M., Zanella, I. et al. Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro. Eur J Nutr 53, 1685–1697 (2014). https://doi.org/10.1007/s00394-014-0675-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00394-014-0675-2