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Timing of nutrient restriction and programming of fetal adipose tissue development

Published online by Cambridge University Press:  07 March 2007

Michael E. Symonds ,
Sarah Pearce ,
Jayson Bispham ,
David S. Gardner  and
Terence Stephenson
Michael E. Symonds*
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, UK
Sarah Pearce
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, UK
Jayson Bispham
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, UK
David S. Gardner
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, UK
Terence Stephenson
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, UK
*
Corresponding author: Dr Michael E. Symonds, fax +002B;44 115 970 9382, Michael.Symonds@nottingham.ac.uk
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Abstract

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It is apparent from epidemiological studies that the timing of maternal nutrient restriction has a major influence on outcome in terms of predisposing the resulting offspring to adult obesity. The present review will consider the extent to which maternal age, parity and nutritional restriction at defined stages of gestation can have important effects on fat deposition and endocrine sensitivity of adipose tissue in the offspring. For example, in 1-year-old sheep the offspring of juvenile mothers have substantially reduced fat deposition compared with those born to adult mothers. Offspring of primiparous adult mothers, however, show increased adiposity compared with those born to multiparous mothers. These offspring of multiparous ewes show retained abundance of the brown adipose tissue-specific uncoupling protein 1 at 1 month of age. A stimulated rate of metabolism in brown fat of these offspring may act to reduce adipose tissue deposition in later life. In terms of defined windows of development that can programme adipose tissue growth, maternal nutrient restriction targetted over the period of maximal placental growth results in increased adiposity at term in conjunction with enhanced abundance of mRNA for the insulin-like growth factor-I and -II receptors. In contrast, nutrient restriction in late gestation, coincident with the period of maximal fetal growth, has no major effect on adiposity but results in greater abundance of specific mitochondrial proteins, i.e. voltage-dependent anion channel and/or uncoupling protein 2. These adaptations may increase the predisposal of these offspring to adult obesity. Increasing maternal nutrition in late gestation, however, can result in proportionately less fetal adipose tissue deposition in conjunction with enhanced abundance of uncoupling protein 1.

Keywords

Maternal nutrient restrictionFetal adipose tissue developmentEndocrine sensitivityAdult obesity
Type
Symposium on ‘Adipose tissue development and the programming of adult obesity’
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 3 , August 2004 , pp. 397 - 403
Copyright
Copyright © The Nutrition Society 2004

References

Arsenijevic, D, Onuma, H, Pecquer, C, Raimbault, S, Manning, BS, Miroux, B, Couplan, E, Alves-Guerra, M-C, Goubern, M, Surwit, R, Bouillaud, F, Richard, D, Collins, S & Ricquier, D (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nature Genetics 26, 435–439.Google Scholar
Bamberger, CM, Schulte, HM & Chrousos, GP (1996) Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocrinology Reviews 17, 245–261.Google Scholar
Barker, DJP, Godfrey, KM, Fall, C, Osmond, C, Winter, PD & Shaheen, SO (1991) Relation of birth weight and childhood respiratory infection to adult lung function and disease from obstructive airways disease. British Medical Journal 303, 671–675.Google Scholar
Bispham, J, Budge, H, Mostyn, A, Dandrea, J, Clarke, L, Keisler, D, Symonds, ME & Stephenson, T (2002) Ambient temperature, maternal dexamethasone, and postnatal ontogeny of leptin in the neonatal lamb. Pediatric Research 52, 85–90.Google Scholar
Bispham, J, Clarke, L, Symonds, ME & Stephenson, T (2003a) Postnatal ontogeny of insulin-like growth factor (IGF) and prolactin receptor (PRL-R) in ovine perirenal adipose tissue. Journal of Physiology (London) 547P, C65.Google Scholar
Bispham, J, Gopalakrishnan, GS, Dandrea, J, Wilson, V, Budge, H, Keisler, DH, Broughton, F, Stephenson, T & Symonds, ME (2003b) Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development. Endocrinology 144, 3575–3585.Google Scholar
Budge, H, Bispham, J, Dandrea, J, Evans, L, Heasman, L, Ingleton, P, Sullivan, C, Wilson, V, Stephenson, T & Symonds, ME (2000) Effect of maternal nutrition on brown adipose tissue and prolactin receptor status in the fetal lamb. Pediatric Research 47, 781–786.Google Scholar
Budge, H, Dandrea, J, Mostyn, A, Evens, Y, Watkins, R, Sullivan, C, Ingleton, P, Stephenson, T & Symonds, ME (2003) Differential effects of fetal number and maternal nutrition in late gestation on prolactin receptor abundance and adipose tissue development in the neonatal lamb. Pediatric Research 53, 302–308.Google Scholar
Budge, H, Edwards, LJ, McMillen, IC, Bryce, A, Warnes, K, Stephenson, T & Symonds, ME (2004) Nutritional manipulation of fetal adipose tissue deposition and uncoupling protein 1 abundance in the fetal sheep; differential effects of timing and duration. Biology of Reproduction (In the Press).Google Scholar
Budge, H, Mostyn, A, Wilson, V, Khong, A, Walker, AM, Symonds, ME & Stephenson, T (2002) The effect of maternal prolactin infusion during pregnancy on fetal adipose tissue development. Journal of Endocrinology 147, 427–433.CrossRefGoogle Scholar
Cassell, PG, Neverova, M, Janmohamed, S, Uwakwe, N, Qureshi, A, McCarthy, MI, Saker, PJ, Albon, L, Kopelman, P, Noonan, K, Easlick, J, Ramachandran, A, Snehalatha, C, Pecqueur, C, Ricquier, D, Warden, C & Hitman, GA (1999) An uncoupling protein 2 gene variant is associated with a raised body mass index but not type II diabetes. Diabetologia 42, 688–692.CrossRefGoogle Scholar
Clarke, L, Bryant, MJ, Lomax, MA & Symonds, ME (1997a) Maternal manipulation of brown adipose tissue and liver development in the ovine fetus during late gestation. British Journal of Nutrition 77, 871–883.CrossRefGoogle ScholarPubMed
Clarke, L, Buss, DS, Juniper, DS, Lomax, MA & Symonds, ME (1997b) Adipose tissue development during early postnatal life in ewe-reared lambs. Experimental Physiology 82, 1015–1017.Google Scholar
Crompton, M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochemical Journal 341, 233–249.Google Scholar
Dandrea, J, Wilson, V, Gopalakrishnan, G, Heasman, L, Budge, H, Stephenson, T & Symonds, ME (2001) Maternal nutritional manipulation of placental growth and glucose transporter-1 abundance in sheep. Reproduction 122, 793–800.Google Scholar
Devasker, SU, Anthony, RV & Hay, WW (2002) Ontogeny and insulin regulation of fetal ovine white adipose tissue leptin expression. American Journal of Physiology 282, R431–R438.Google Scholar
Forhead, AJ, Thomas, L, Crabtree, J, Hoggard, N, Gardner, DS, Giussani, DA & Fowden, AL (2002) Plasma leptin concentrations in fetal sheep during late gestation: ontogeny and effect of glucocorticoids. Endocrinology 275, 1166–1173.Google Scholar
Gemmel, RT, Bell, AW & Alexander, G (1972) Morphology of adipose cells in lambs at birth and during subsequent transition of brown to white adipose tissue in cold and in warm conditions. American Journal of Anatomy 133, 143–164.Google Scholar
Godfrey, K, Robinson, S, Barker, DJP, Osmond, C & Cox, V (1996) Maternal nutrition in early and late pregnancy in relation to placental and fetal growth. British Medical Journal 312, 410–414.Google Scholar
Gopalakrishnan, G, Rhind, SM, Stephenson, T, Kyle, CE, Brooks, AN, Rae, MT & Symonds, ME (2001) Effect of maternal nutrient restriction at defined periods in early to mid gestation on placento-fetal, kidney and adipose tissue weights at 110 days gestation in sheep. Early Human Development 63, 58–59.Google Scholar
Gottlieb, RA (2000) Mitochondria: execution central. FEBS Letters 482, 6–12.Google Scholar
Heasman, L, Brameld, JM, Mostyn, A, Budge, H, Dawson, J, Buttery, PJ, Stephenson, T & Symonds, ME (2000) Maternal nutrient restriction during early to mid gestation alters the relationship between IGF-I and body size at term in fetal sheep. Reproduction, Fertility and Development 12, 345–350.CrossRefGoogle ScholarPubMed
Howe, DC, Gertler, A & Challis, JRG (2002) The late gestation increase in circulating ACTH and cortisol in the fetal sheep is suppressed by intracerebroventricular infusion of recombinant ovine leptin. Journal of Endocrinology 170, 259–266.Google Scholar
Lean, MEJ (1989) Brown adipose tissue in humans. Proceedings of the Nutrition Society 48, 243–256.CrossRefGoogle ScholarPubMed
Lorenzo, M, Valverde, AM, Teurel, T & Benito, M (1993) IGF-I is a mitogen involved in differentiation-related gene expression in fetal brown adipocytes. Journal of Cell Biology 123, 1567–1575.Google Scholar
Lowell, BB, S-Susulic, V, Hamann, A, Lawitts, JA, Himms-Hagen, J, Boyer, BB, Kozak, LP & Flier, JS (1993) Development of obesity in transgenenic mice after genetic ablation of brown adipose tissue. Nature 366, 740–742.Google Scholar
Lumey, LH & Stein, AD (1997) Offspring birthweights after maternal intrauterine undernutrition: a comparison within sibships. American Journal of Epidemiology 146, 810–819.Google Scholar
Masuzaki, H, Paterson, J, Shinyama, H, Morton, NM, Mullins, JJ, Seckl, JR & Flier, JS (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294, 2166–2170.CrossRefGoogle ScholarPubMed
Mostyn, A, Wilson, V, Dandrea, J, Yakubu, DP, Budge, H, Alves-Guerra, MC, Pecqueur, C, Miroux, B, Symonds, ME & Stephenson, T (2003) Ontogeny and nutritional manipulation of mitochondrial protein abundance in adipose tissue and the lungs of postnatal sheep. British Journal of Nutrition 90, 323–328.Google Scholar
Moulin, K, Truel, N, Andre, M, Arnauld, E, Nibbelink, M, Cousin, B, Dani, C, Penicaud, L & Casteilla, L (2001) Emergence during development of the white-adipocyte cell phenotype is independent of the brown-adipocyte cell phenotype. Biochemical Journal 356, 659–664.Google Scholar
Mulhlauser, BS, Roberts, CT, McFarlane, J, Kauter, KG & McMillen, IC (2002) Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements. Biology of Reproduction 67, 493–499.Google Scholar
Owens, JA, Kind, KL, Carbone, F, Robinson, JS & Owens, PC (1994) Circulating insulin-like growth factors-I and -II and substrates in fetal sheep following restriction of placental growth. Journal of Endocrinology 140, 5–13.Google Scholar
Pearce, S, Dandrea, J, Symonds, ME & Stephenson, T (2002) Comparison of adipose tissue and organ deposition between singleton and twin lambs at one month of age. Proceedings of the Nutrition Society 61, 132A.Google Scholar
Pearce, S, Wang, J, Symonds, ME & Stephenson, T (2003) Effect of maternal parity on adipose tissue development in the resulting offspring. Pediatric Research 53, Suppl.40A.Google Scholar
Roseboom, TJ (2000) Prenatal exposure to the Dutch famine and health in later life. PhD Thesis, University of Amsterdam, The Netherlands.Google Scholar
Roseboom, TJ, van der Meulen, JHP, Osmond, C, Barker, DJP, Ravelli, ACJ & Blecker, OP (2000a) Plasma lipid profile in adults after perinatal exposure to famine. American Journal of Clinical Nutrition 72, 1101–1106.Google Scholar
Roseboom, TJ, van der Meulen, JHP, Osmond, C, Barker, DJP, Ravelli, ACJ, Schroeder-Tanka, JM von Montfrans, GA, Michels, RPJ & Blecker, OP (2000b) Coronary heart disease in adults after perinatal exposure to the Dutch famine, 1944–45. Heart 84, 595–598.Google Scholar
Stevens, D, Alexander, G & Bell, AW (1990) Effects of prolonged glucose infusion into fetal sheep on body growth, fat deposition and gestation length. Journal of Developmental Physiology 13, 277–281.Google ScholarPubMed
Stewart, PM & Krozowski, ZS (1999) 11β-Hydroxysteroid dehydrogenase. Vitamins and Hormones 57, 249–324.Google Scholar
Symonds, ME, Bryant, MJ, Clarke, L, Darby, CJ & Lomax, MA (1992) Effect of maternal cold exposure on brown adipose tissue and thermoregenesis in the neonatal lamb. Journal of Physiology (London) 455, 487–502.CrossRefGoogle ScholarPubMed
Symonds, ME, Gardner, DS, Pearce, S & Stephenson, T (2004) Endocrine responses to fetal undernutrition: the growth hormone (GH): insulin-like growth factor (IGF) axis. In Fetal Nutrition and Adult Disease – Programming of Chronic Disease Through Fetal Exposure to Undernutrition, pp. 353–380 [Langley-Evans, SC, editor]. Wallingford, Oxon.: CAB International.CrossRefGoogle Scholar
Symonds, ME & Lomax, MA (1992) Maternal and environmental influences on thermoregulation in the neonate. Proceedings of the Nutrition Society 51, 165–172.Google Scholar
Symonds, ME, Mostyn, A, Pearce, S, Budge, H & Stephenson, T (2003) Energy regulation in the fetus: endocrine control of adipose tissue development. Journal of Endocrinology 179, 293–299.Google Scholar
Symonds, ME, Phillips, ID, Anthony, RV, Owens, JA & McMillen, IC (1998) Prolactin receptor gene expression and foetal adipose tissue. Journal of Neuroendocrinology 10, 885–890.CrossRefGoogle ScholarPubMed
Symonds, ME & Stephenson, T (1999) Maternal nutrient restriction and endocrine programming of fetal adipose tissue development. Biochemical Society Transactions 27, 97–103.CrossRefGoogle Scholar
Teruel, T, Valverde, AM, Benito, M & Lorenzo, M (1996) Insulin-like growth factor and insulin induce adipogenic-related gene expression in fetal brown adipocyte primary cultures. Biochemical Journal 319, 627–632.Google Scholar
Thompson, GE, Bassett, JM, Samson, DE & Slee, J (1982) The effect of cold exposure of pregnant sheep on fetal plasma nutrients, hormones and birth weight. British Journal of Nutrition 48, 59–64.Google Scholar
Voehringer, DW, Hirschberg, DL, Xiao, J, Lu, Q, Roederer, M, Lock, CB, Herzenberg, LA, Steinman, L & Herzenberg, LA (2000) Gene microarray identification of redox and mitochondrial elements that control resistance or sensitivity to apoptosis. Proceedings of the National Academy of Sciences USA 97, 2680–2685.CrossRefGoogle ScholarPubMed
Whorwood, CB, Firth, KM, Budge, H & Symonds, ME (2001) Maternal undernutrition during early- to mid-gestation programmes tissue-specific alterations in the expression of the glucocorticoid receptor, 11β-hydroxysteroid dehydrogenase isoforms and type 1 angiotensin II receptor in neonatal sheep. Endocrinology 142, 1778–1785.CrossRefGoogle Scholar
Young, L, Fernandes, K, McEvoy, T, Butterwith, S, Gutierrez, C, Carolan, C, Broadbent, P, Robinson, J, Wilmut, I & Sinclair, K (2001) Epigenetic change in IGF2R is associated with fetal overgrowth after embryo culture. Nature Genetics 27, 153–154.CrossRefGoogle ScholarPubMed
Yuen, BS, Owens, PC, Muhlhausler, BS, Roberts, CT, Symonds, ME, Keisler, DH, McFarlane, JR, Kauter, KG, Evens, Y & McMillen, IC (2003) Leptin alters the structural and functional characteristics of adipose tissue before birth. FASEB Journal 17, 1102–1104.CrossRefGoogle ScholarPubMed
Yuen, BSJ, McMillen, IC, Symonds, ME & Owens, PC (1999) Abundance of leptin messenger ribonucleic acid in fetal adipose tissue is related to fetal body weight. Journal of Endocrinology 163, R1–R4.Google Scholar
Yuen, BSJ, Owens, PC, McFarlane, J, Symonds, ME, Edwards, LJ, Kauter, KG & McMillen, IC (2002) Circulating leptin concentrations are positively related to leptin mRNA expression in fetus adipose tissue in the pregnant ewe fed at or below maintenance energy requirements during late gestation. Biology of Reproduction 67, 911–916.Google Scholar