Abstract
Flaxseed has several benefits for health such as improvement in lipid profile; and since thyroid hormones increases cholesterol biliary excretion, we decide to evaluate the programming effect of maternal flaxseed diet during lactation upon thyroid hormone metabolism and action in the adult offspring in rats. At birth, lactating rats were divided into: flaxseed dams (F) – diet with 25% of flaxseed – and controls dams (C). F and C pups received normal diet after weaning and male offspring were sacrificed at 21 and 180 days old. We evaluated serum T3, T4, and TSH; type 1 and 2 deiodinase activities (D1 and D2) in the liver, thyroid, brown adipose tissue (BAT), and pituitary; thyroid hormone receptor (TRβ1) expression and mitochondrial glycerophosphate-dehydrogenase activity (GPDm) in the liver. F offspring showed lower T3 levels at weaning (−30%, p<0.05) probably caused by lower liver D1 activity (−32%, p<0.05) and higher TSH levels (+84.6%, p<0.05) characterizing a profile of hypothyroidism. At 180 days old, F offspring had lower T4 and thyroid D1 and D2 activities (−28.3%, −18.5%, and −44.2%, respectively, p<0.05) and higher BAT D2 activity (+34.5%, p<0.05). We suggest that adult F animals present an inappropriate TSH action on the thyroid, since thyroid deiodinase was lower. Serum T3 was normal probably due to a higher BAT D2 activity and may reflect the tissue T3 concentration because liver D1, TRβ1, and GPDm were normal. Thus, maternal flaxseed diet during lactation may affect the thyroid hormones metabolism in a long-term.
Key words
flaxseed - lactation - programming - deiodinase - thyroid hormones
References
1
Prasad K.
Flaxseed and cardiovascular health.
J Cardiovasc Pharmacol.
2009;
54
369-377
2
Cunnane SC, Ganguli S, Menard C, Liede AC, Hamadeh MJ, Chen ZY, Wolever TM, Jenkins DJ.
High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans.
Br J Nutr.
1993;
69
443-453
3
Tou JCL, Chen J, Thompson LU.
Flaxseed and its lignan precursor, secoisolariciresinol diglycoside, affect pregnancy outcome and reproductive development in rats.
J Nutr.
1998;
128
1861-1868
4
Collins TFX, Sprando RL, Black TN, Olejnik N, Wiesenfeld PW, Babu US, Bryant M, Flynn TJ, Ruggles DI.
Effects of flaxseed and defatted flaxseed meal on reproduction and development in rats.
Food Chem Toxicol.
2003;
41
819-834
5
Tou JCL, Thompson LU.
Exposure to flaxseed or it lignan component during different developmental stages influences rat mammary gland structures.
Carcinogenesis.
1999;
20
1831-1835
6
Lucas A.
Long-term programming effects of early nutrition – implications for the preterm infant.
J Perinatol.
2005;
25
2-6
7
de Moura EG, Lisboa PC, Passos MC.
Neonatal programming of neuroimmunomodulation – role of adipocytokines and neuropeptides.
Neuroimmunomodulation.
2008;
15
176-188
8
Passos MCF, Ramos CF, Moura EG.
Short and long term effects of malnutrition in rats during lactation on the body weight of offspring.
Nutr Res.
2000;
20
1603-1612
9
Moura EG, Santos RS, Lisboa PC, Alves SB, Bonomo IT, Fagundes AT, Oliveira E, Passos MC.
Thyroid function and body weight programming by neonatal hyperthyroidism in rats – the role of leptin and deiodinase activities.
Horm Metab Res.
2008;
40
1-7
10
Toste FP, Moura EG, Lisboa PC, Fagundes AT, Oliveira E, Passos MCF.
Neonatal leptin treatment programmes leptin hypothalamic resistance and intermediary metabolic parameters in adult rats.
Br J Nutr.
2006a;
95
830-837
11
Bonomo IT, Lisboa PC, Pereira AR, Passos MCF, Moura EG.
Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring.
J Endocrinol.
2007;
192
339-344
12
Oliveira E, Moura EG, Santos-Silva AP, Fagundes AT, Rios AS, Abreu-Villaça Y, Nogueira Neto JF, Passos MC, Lisboa PC.
Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring.
J Endocrinol.
2009;
202
397-405
13
Troina AA, Figueiredo MS, Moura EG, Boaventura GT, Soares LL, Cardozo LF, Oliveira E, Lisboa PC, Passos MA, Passos MC.
Maternal flaxseed diet during lactation alters milk composition and programs the offspring body composition, lipid profile and sexual function.
Food Chem Toxicol.
2010;
48
697-703
14
Figueiredo MS, de Moura EG, Lisboa PC, Troina AA, Trevenzoli IH, Oliveira E, Boaventura GT, da Fonseca Passos MC.
Flaxseed supplementation of rats during lactation changes the adiposity and glucose homeostasis of their offspring.
Life Sci.
2009;
85
365-371
15
Rodrigues AL, de Moura EG, Passos MC, Dutra SC, Lisboa PC.
Postnatal early overnutrition changes the leptin signalling pathway in the hypothalamic-pituitary-thyroid axis of young and adult rats.
J Physiol.
2009;
587
2647-2661
16
Bonomo IT, Lisboa PC, Passos MC, Alves SB, Reis AM, de Moura EG.
Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat.
J Endocrinol.
2008;
198
331-337
17
Lisboa PC, Fagundes AT, Denolato AT, Oliveira E, Bonomo IT, Alves SB, Curty FH, Passos MC, Moura EG.
Neonatal low-protein diet changes deiodinase activities and pituitary TSH response to TRH in adult rats.
Exp Biol Med.
2008;
233
57-63
18
Toste FP, Alves SB, Dutra SCP, Bonomo IT, Lisboa PC, Moura EG, Passos MC.
Temporal evaluations of the thyroid function of rats programmed by leptin treatment on the neonatal period.
Horm Metab Res.
2006;
38
827-831
19
Dutra SCP, Passos MCF, Lisboa PC, Santos RS, Cabanelas AP, Pazos-Moura CC, Moura EG.
Liver deiodinase activity is increased in adult rats whose dams were submitted to malnutrition during lactation.
Horm Metab Res.
2003;
35
268-270
20
Bianco AC, Salvatore D, Gereben B, Berry M, Larsen PR.
Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.
Endocr Rev.
2002;
23
38-89
21
Lee YP, Lardy HA.
Influence of thyroid hormones on L-GPD and other dehydrogenases in various organs of the rat.
J Biol Chem.
1965;
240
1427-1436
22
Müller S, Seitz HJ.
Cloning of a cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase from rat liver and its regulation by thyroid hormones.
Proc Natl Acad Sci USA.
1994;
25
10581-10585
23
DosSantos RA, Alfadda A, Eto K, Kadowaki T, Silva JE.
Evidence for a compensated thermogenic defect in transgenic mice lacking the mitochondrial glycerol-3-phosphate dehydrogenase gene.
Endocrinology.
2003;
144
5469-5479
24
Koza RA, Kozak UC, Brown LJ, Leiter EIL, MacDonald MJ, Kozak LP.
Sequence and tissue-dependent RNA expression of mouse FAD-linked glycerol-3-phosphate dehydrogenase.
Arch Biochem Biophys.
1996;
336
97-104
25
Forrest D, Hanebuth E, Smeyne RJ, Everds N, Stewart CL, Wehner JM, Curran T.
Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: evidence for tissue-specific modulation of receptor function.
EMBO J.
1996;
15
3006-3015
26
Marques RG, Morales MM, Petroianu A.
Brazilian law for scientific use of animals.
Acta Cir Bras.
2009;
24
69-74
27
Fishbeck KL, Rasmussen KM.
Effect of repeated cycles on maternal nutritional status, lactational performance and litter growth in ad libitum-fed and chronically food-restricted rats.
J Nutr.
1987;
117
1967-1975
28
Reeves PG, Nielsen FH, Fahey Jr GC.
AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76 rodent diet.
J Nutr.
1993;
123
1939-1951
29
Pazos-Moura CC, Moura EG, Dorris ML, Rehnmark S, Melendez L, Silva JE, Taurog A.
Effect of iodine deficiency and cold exposure on thyroxine 5′-deiodinase activity in various rat tissues.
Am J Physiol.
1991;
260
175-182
30
Curty FH, Lisbôa PC, Ortiga-Carvalho TM, Pazos-Moura CC.
The somatostatin analogue octreotide modulates Iodothyronine deiodinase activity and pituitary neuromedin B.
Thyroid.
2000;
10
647-652
31
Lisbôa PC, Curty FH, Moreira RM, Oliveira KJ, Pazos-Moura CC.
Sex steroids modulate rat anterior pituitary and liver iodothyronine deiodinase activities.
Horm Metab Res.
2001;
33
532-535
32
Bradford MM.
A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding.
Anal Biochem.
1976;
72
248-254
33
Oliveira E, Fagundes AT, Alves SB, Pazos-Moura CC, Moura EG, Passos MC, Lisboa PC.
Chronic leptin treatment inhibits liver mitochondrial alpha-glycerol-beta-phosphate dehydrogenase in euthyroid rats.
Horm Metab Res.
2007;
39
867-870
34
Cabanelas A, Lisboa PC, Moura EG, Pazos-Moura CC.
Leptin acute modulation of the 5′-deiodinase activities in hypothalamus, pituitary and brown adipose tissue of fed rats.
Horm Metab Res.
2006;
38
481-485
35
Oliveira JH, Persani L, Beck-Peccoz P, Abucham J.
Investigating the paradox of hypothyroidism and increased serum thyrotropin (TSH) levels in Sheehan's syndrome: characterization of TSH carbohydrate content and bioactivity.
J Clin Endocrinol Metab.
2001;
86
1694-1699
36
Pazos-Moura CC, Ortiga-Carvalho TM, de Moura EG.
The autocrine/paracrine regulation of thyrotropin secretion.
Thyroid.
2003;
13
167-175
37
Oliveira KJ, Cabanelas A, Veiga MA, Paula GS, Ortiga-Carvalho TM, Wada E, Wada K, Pazos-Moura CC.
Impaired serum thyrotropin response to hypothyroidism in mice with disruption of neuromedin B receptor.
Regul Pept.
2008;
146
213-217
38
Alrefai H, Allababidi H, Levy S, Levy J.
The endocrine system in diabetes mellitus.
Endocrine.
2002;
18
105-119
39
Bianco AC, Kim BW.
Deiodinases: implications of the local control of thyroid hormone action.
J Clin Invest.
2006;
116
2571-2579
40
Mebis L, Langouche L, Visser TJ, Van den Berghe G.
The type II iodothyronine deiodinase is up-regulated in skeletal muscle during prolonged critical illness.
J Clin Endocrinol Metab.
2007;
92
3330-3333
41
Passos MC, da Fonte Ramos C, Dutra SC, Mouço T, de Moura EG.
Long term effects of malnutrition during lactation on the thyroid function of offspring.
Horm Metab Res.
2002;
34
40-43
42
Teixeira CV, Ramos CD, Mouco T, Passos MC, De Moura EG.
Leptin injection during lactation alters thyroid function in adult rats.
Horm Metab Res.
2003;
35
367-371
43
Waterland RA.
Early environmental effects on epigenetic regulation in humans.
Epigenetics.
2009;
4
523-525
44
Waterland RA.
Is epigenetics an important link between early life events and adult disease?.
Horm Metab Res.
2009;
1
13-16
Correspondence
Prof. E. G. de MouraPhD
Departamento de Ciências
Fisiológicas – 5 ° andar
Instituto de Biologia
Universidade do Estado do
Rio de Janeiro
Av. 28 de setembro
87-Rio de Janeiro
RJ 20551-030
Brazil
Phone: +55/21/2587 6434
Fax: +55/21/2587 6129
Email: egbertomoura@globo.com