Developmental Plasticity of Endocrine Disorders in Obesity Model Primed by Early Weaning in Dams

N. S. Lima; E. G. Moura; J. G. Franco; C. R. Pinheiro; C. C. Pazos-Moura; A. Cabanelas; A. S. Carlos; C. C. Nascimento-Saba; E. de Oliveira; P. C. Lisboa

doi:10.1055/s-0032-1323703

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2013; 45(01): 22-30
DOI: 10.1055/s-0032-1323703

Original Basic

Developmental Plasticity of Endocrine Disorders in Obesity Model Primed by Early Weaning in Dams

Authors

N. S. Lima

¹Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
E. G. Moura

¹Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
J. G. Franco

¹Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
C. R. Pinheiro

¹Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
C. C. Pazos-Moura

²Laboratory of Molecular Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
A. Cabanelas

²Laboratory of Molecular Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
A. S. Carlos

³Laboratory of Morphofunctional Analysis, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
C. C. Nascimento-Saba

³Laboratory of Morphofunctional Analysis, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
E. de Oliveira

¹Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
P. C. Lisboa

¹Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil

Abstract

Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning) – dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control – dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area ( − 67.7% and − 62%, respectively), body fat mass ( − 26%), and leptin expression in visceral adipocyte ( − 64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 ( − 55%) and TSH ( − 44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRβ3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue ( − 40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.

Key words

early weaning - obesity - leptin - adrenal - thyroid

Full Text

References

References
1 World Health Organization . Breastfeeding: a vital emergency response. Are you ready?. Geneva: WHO; 2009
2 Harder T, Bergmann R, Kallischnigg G, Plagemann A. Duration of breastfeeding and risk of overweight: a meta-analysis. Am J Epidemiol 2005; 162: 397-403
3 Barker DJ. The developmental origins of adult disease. Eur J Epidemiol 2004; 18: 733-736
4 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 – role of leptin and deiodinase activities. Horm Metab Res 2008; 40: 1-7
5 Gluckman PD, Hanson MA. Developmental plasticity and human disease: research directions. J Intern Med 2007; 261: 461-471
6 Passos MC, Vicente LL, Lisboa PC, Moura EG. Absence of anorectic effect to acute peripheral leptin treatment in adult rats whose mothers were malnourished during lactation. Horm Metab Res 2004; 36: 625-629
7 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 (Maywood) 2008; 233: 57-63
8 Fagundes AT, Moura EG, Passos MC, Oliveira E, Toste FP, Bonomo IT, Trevenzoli IH, Garcia RM, Lisboa PC. Maternal low-protein diet during lactation programmes body composition and glucose homeostasis in the adult rat offspring. Br J Nutr 2007; 98: 922-928
9 de Moura EG, Bonomo IT, Nogueira-Neto JF, de Oliveira E, Trevenzoli IH, Reis AM, Passos MC, Lisboa PC. Maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny. J Physiol 2009; 587: 4919-4929
10 Lima NS, de Moura EG, Passos MC, Nogueira Neto FJ, Reis AM, de Oliveira E, Lisboa PC. Early weaning causes undernutrition for a short period and programmes same metabolic syndrome components and leptin resistance in adult rat offspring. Br J Nutr 2011; 105: 1405-1413
11 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
12 Matsuzawa Y. Therapy insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med 2006; 3: 35-42
13 Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 2008; 93: S64-S73
14 Ahima RS. Adipose tissue as an endocrine organ. Obesity 2006; 14: 242S-249S
15 Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-770
16 dos Santos Oliveira L, de Lima DP, da Silva AA, da Silva MC, de Souza SL, Manhães-de-Castro R. Early weaning programs rats to have a dietary preference for fat and palatable foods in adulthood. Behav Processes 2011; 286: 75-80
17 Osaki LH, Curi MAF, Alvares EP, Gama P. Early weaning accelerates the differentiation of mucous neck cells in rat gastric mucosa: possible role of TGFalpha/EGFR. Differentiation 2010; 79: 48-56
18 de Oliveira E, Moura EG, Santos-Silva AP, Pinheiro CR, Lima NS, Nogueira-Neto JF, Nunes-Freitas AL, Abreu-Villaça Y, Passos MC, Lisboa PC. Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rat offspring. J Endocrinol 2010; 206: 55-63
19 Pinheiro CR, Oliveira E, Trevenzoli IH, Manhães AC, Santos-Silva AP, Younes-Rapozo V, Claudio-Neto S, Santana AC, Nascimento-Saba CC, Moura EG, Lisboa PC. Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats. Horm Metab Res 2011; 43: 693-701
20 Nobre JL, Lisboa PC, Santos-Silva AP, Lima NS, Manhães AC, Nogueira-Neto JF, Cabanelas A, Pazos-Moura CC, Moura EG, de Oliveira E. Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotineexposure. J Endocrinol 2011; 210: 349-359
21 Conceição EP, Trevenzoli IH, Oliveira E, Franco JG, Carlos AS, Nascimento-Saba CC, Moura EG, Lisboa PC. Higher white adipocyte area and lower leptin production in adult rats overfed during lactation. Horm Metab Res 2011; 43: 513-516
22 Trevenzoli IH, Rodrigues AL, Oliveira E, Thole AA, Carvalho L, Figueiredo MS, Toste FP, Neto JF, Passos MC, Lisboa PC, Moura EG. Leptin treatment during lactation programs leptin synthesis, intermediate metabolism, and liver microsteatosis in adult rats. Horm Metab Res 2010; 42: 483-490
23 Paz-Filho GJ, Volaco A, Suplicy HL, Radominski RB, Boguszewski CL. Decrease in leptin production by the adipose tissue in obesity associated with severe metabolic syndrome. Arq Bras Endocrinol Metabol 2009; 53: 1088-1095
24 Valzelli L. The “isolation syndrome” in mice. Psychopharmacology 1973; 31: 305-320
25 Lukaski HC, Hall CB, Marchello MJ, Siders WA. Validation of dual X-ray absorptiometry for body-composition assessment of rats exposed to dietary stressors. Nutrition 2001; 17: 607-613
26 Glickman SG, Marn CS, Supiano MA, Dengel DR. Validity and reliability of dual-energy X-ray absorptiometry for the assessment of abdominal adiposity. J Appl Physio 2004; 97: 509-514
27 Akamine R, Yamamoto T, Watanabe M, Yamazaki N, Kataoka M, Ishikawa M, Ooie T, Baba Y, Shinohara Y. Usefulness of the 5′ region of the cDNA encoding acidic ribosomal phosphoprotein P0 conserved among rats, mice, and humans as a standard probe for gene expression analysis in different tissues and animal species. J Biochem Biophys Meth 2007; 70: 481-486
28 Cabanelas A, Cordeiro A, Santos Almeida NA, Monteiro de Paula GS, Coelho VM, Ortiga-Carvalho TM, Pazos-Moura CC. Effect of triiodothyronine on adiponectin expression and leptin release by white adipose tissue of normal rats. Horm Metab Res 2010; 42: 254-260
29 Van de Woestijne AP, Monajemi H, Kalkhoven E, Visseren FL. Adipose tissue dysfunction and hypertriglyceridemia: mechanisms and management. Obes Ver 2011; 12: 829-840
30 Prior LJ, Velkoska E, Watts R, Cameron-Smith D, Morris MJ. Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition: a protective effect?. Int J Obes 2008; 32: 1585-1594
31 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
32 Rodrigues AL, de Moura EG, Passos MC, Dutra SC, Lisboa PC. Postnatal early overnutrition changes the leptin signaling pathway in the hypothalamic-pituitary-thyroid axis of young and adult rats. J Physiol 2009; 587: 2647-2661
33 Young JB. Programming of sympathoadrenal function. Trends Endocrinol Metab 2002; 13: 381-385
34 Martins AC, Souza KL, Shio MT, Mathias PC, Lelkes PI, Garcia RM. Adrenal medullary function and expression of catecholamine-synthesizing enzymes in mice with hypothalamic obesity. Life Sci 2004; 74: 3211-3222
35 Bonomo IT, Lisboa PC, Pereira AR, Passos MC, de Moura EG. Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring. J Endocrinol 2007; 192: 339-344
36 Moura EG, Ramos CF, Nascimento CC, Rosenthal D, Breitenbach MM. Thyroid function in fasting rats: variations in ¹³¹I uptake and transient decrease in peroxidase activity. Braz J Med Biol Res 1987; 20: 407-410
37 Légrádi G, Emerson CH, Ahima RS, Flier JS, Lechan RM. Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology 1997; 138: 2569-2576
38 Ortiga-Carvalho TM, Oliveira KJ, Soares BA, Pazos-Moura CC. The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol 2002; 174: 121-125
39 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
40 Lisboa PC, Oliveira KJ, Cabanelas A, Ortiga-Carvalho TM, Pazos-Moura CC. Acute cold exposure, leptin, and somatostatin analog (octreotide) modulate thyroid 5′-deiodinase activity. Am J Physiol Endocrinol Metab 2003; 284: E1172-E1176
41 Bonomo IT, Lisboa PC, Passos MC, Pazos-Moura CC, Reis AM, Moura EG. Prolactin inhibition in lactating rats changes leptin transfer through the milk. Horm Metab Res 2005; 37: 220-225
42 Toste FP, Alves SB, Dutra SC, Bonomo IT, Lisboa PC, Moura EG, Passos MC. Temporal evaluation of the thyroid function of rats programmed by leptin treatment on the neonatal period. Horm Metab Res 2006; 38: 827-831
43 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
44 Dallman MF. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab 2010; 21: 159-165
45 Kikusui T, Nakamura K, Kakuma Y, Mori Y. Early weaning augments neuroendocrine stress responses in mice. Behav Brain Res 2006; 175: 96-103
46 Ono M, Kikusui T, Sasaki N, Ichikawa M, Mori Y, Murakami-Murofushi K. Early weaning induces anxiety and precocious myelination in the anterior part of the basolateral amygdala of male balb/c mice. Neuroscience 2008; 156: 1103-1110
47 Ito A, Kikusui T, Takeuchi Y, Mori Y. Effects of early weaning on anxiety and autonomic responses to stress in rats. Behav Brain Res 2006; 171: 87-93
48 Rosmond R, Dallman MF, Björntorp P. Stress-related cortisol secretion in men: relationship with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 1998; 83: 1853-1859
49 Bertagna X, Guignat L, Groussin L, Bertherat J. Cushing’s disease. Best Prac Res Clin Endocrinol Metab 2009; 23: 607-623
50 Livingstone DE, Kenyon CJ, Walker BR. Mechanisms of dysregulation of 11 beta-hydroxysteroid dehydrogenase type 1 in obese Zucker rats. J Endocrinol 2000; 167: 533-539
51 Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001; 294: 2166-2170
52 Vieau D, Sebaai N, Léonhardt M, Dutriez-Casteloot I, Molendi-Coste O, Laborie C, Breton C, Deloof S, Lesage J. HPA axis programming by maternal undernutrition in the male rat offspring. Psychoneuroendocrinology 2007; 32: S16-S20
53 Trevenzoli IH, Valle MM, Machado FB, Garcia RM, Passos MC, Lisboa PC, Moura EG. Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters. J Physiol 2007; 580: 629-637
54 Masuo K, Rakugi H, Ogihara T, Esler MD, Lambert GW. Cardiovascular and renal complications of type 2 diabetes in obesity: role of sympathetic nerve activity and insulin resistance. Curr Diabetes Rev 2010; 6: 58-67
55 Mauso K, Lambert GW. Relationships of Adrenoceptor Polymorphisms with Obesity. J Obes 2011; 1-10
56 Clément K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD. Genetic variation in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 1995; 333: 352-354