Hostname: page-component-745bb68f8f-b95js Total loading time: 0 Render date: 2025-01-24T00:30:20.046Z Has data issue: false hasContentIssue false
  • English
  • Français

Nutritional regulation of fetal growth and implications for productive life in ruminants

Published online by Cambridge University Press:  23 March 2010

M. E. Symonds ,
S. P. Sebert  and
H. Budge
M. E. Symonds*
Affiliation:
Early Life Nutrition Research Unit, Respiratory Biomedical Research Unit, Academic Child Health, School of Clinical Sciences, University Hospital, Nottingham, NG7 2UH, United Kingdom
S. P. Sebert
Affiliation:
Early Life Nutrition Research Unit, Respiratory Biomedical Research Unit, Academic Child Health, School of Clinical Sciences, University Hospital, Nottingham, NG7 2UH, United Kingdom
H. Budge
Affiliation:
Early Life Nutrition Research Unit, Respiratory Biomedical Research Unit, Academic Child Health, School of Clinical Sciences, University Hospital, Nottingham, NG7 2UH, United Kingdom
*
†E-mail: [email protected]
Get access

Abstract

The maternal nutritional and metabolic environment is critical in determining not only the reproductive success but also the long-term health and viability of the offspring. Changes in maternal diet at defined stages of gestation coincident with different stages of development can have pronounced effects on organ and tissue function in later life. This includes adipose tissue for which differential effects are observed between brown and white adipose tissues. One early, critical window of organ development in the ruminant relates to the period covering uterine attachment, or implantation, and rapid placental growth. During this period, there is pronounced cell division within developing organelles in many fetal tissues, leading to their structural development. In sheep, a 50% global reduction in caloric intake over this specific period profoundly affects placental growth and morphology, resulting in reduced placentome weight. This occurs in conjunction with a lower capacity to inactivate maternal cortisol through the enzyme 11β-hydroxysteroid dehydrogenase type 2 in response to a decrease in maternal plasma cortisol in early gestation. The birth weight of the offspring is, however, unaffected by this dietary manipulation and, although they possess more fat, this adaptation does not persist into adulthood when they become equally obese as those born to control fed mothers. Subsequently, after birth, further changes in fat development occur which impact on both glucocorticoid action and inflammatory responses. These adaptations can include changes in the relative populations of both brown and white adipocytes for which prolactin acting through its receptor appears to have a prominent role. Earlier when in utero nutrient restricted (i.e. between early-to-mid gestation) offspring are exposed to an obesogenic postnatal environment; they exhibit an exaggerated insulin response, which is accompanied by a range of amplified and thus, adverse, physiological or metabolic responses to obesity. These types of adaptations are in marked contrast to the effect of late gestational nutrient restriction, which results in reduced fat mass at birth. As young adults, however, fat mass is increased and, although basal insulin is unaffected, these offspring are insulin resistant. In conclusion, changes in nutrient supply to either the mother and/or her fetus can have profound effects on a range of metabolically important tissues. These have the potential to either exacerbate, or protect from, the adverse effects of later obesity and accompanying complications in the resulting offspring.

Keywords

pregnancygrowthadipose tissuehormones
Type
Full Paper
Information
animal , Volume 4 , Issue 7: XIth International Symposium on Ruminant Physiology (ISRP), 6–9 September, 2009 Clermont-Ferrand (France) , July 2010 , pp. 1075 - 1083
Copyright
Copyright © The Animal Consortium 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agricultural and Food Research Council 1993. Technical committee on responses to nutrients. Report no. 9. Technical committee on responses to nutrients. Report no. 9. CAB International, Wallingford, UK.Google Scholar
Agricultural Research Council 1980. Requirements for energy. The nutritional requirements of ruminant livestock. Commonwealth Agricultural Bureau, Slough, UK.Google Scholar
Au-Yong, IT, Thorn, N, Ganatra, R, Perkins, AC, Symonds, ME 2009. Brown adipose tissue and seasonal variation in humans. Diabetes 58, 2583–2587.CrossRefGoogle ScholarPubMed
Bassett, JM, Bomford, J, Mott, JC 1988. Photoperiod: an important regulator of plasma prolactin concentration in fetal lambs during late gestation. Quarterly Journal of Experimental Physiology 73, 241–244.CrossRefGoogle ScholarPubMed
Bignon, C, Binart, N, Ormandy, C, Schuler, LA, Kelly, PA, Djiane, J 1997. Long and short forms of the ovine prolactin receptor: cDNA cloning and genomic analysis reveal that the two forms arise by different alternative splicing mechanisms in ruminants and in rodents. Journal of Molecular Endocrinology 19, 109–120.CrossRefGoogle ScholarPubMed
Bispham, J, Gopalakrishnan, GS, Dandrea, J, Wilson, V, Budge, H, Keisler, DH, Broughton Pipkin, F, Stephenson, T, Symonds, ME 2003. 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.CrossRefGoogle ScholarPubMed
Bispham, J, Gardner, DS, Gnanalingham, MG, Stephenson, T, Symonds, ME, Budge, H 2005. Maternal nutritional programming of fetal adipose tissue development: differential effects on messenger ribonucleic acid abundance for uncoupling proteins and peroxisome proliferator-activated and prolactin receptors. Endocrinology 146, 3943–3949.CrossRefGoogle ScholarPubMed
Bloomfield, FH, Oliver, MH, Hawkins, P, Campbell, M, Phillips, DJ, Gluckman, PD, Challis, JR, Harding, JE 2003. A periconceptional nutritional origin for noninfectious preterm birth. Science 300, 606.CrossRefGoogle ScholarPubMed
Brennan, KA, Gopalakrishnan, GS, Kurlak, L, Rhind, SM, Brooks, AN, Rae, MT, Olson, DM, Stephenson, T, Symonds, ME 2005. Impact of maternal undernutrition and fetal number on glucocorticoid, growth hormone and insulin-like growth factor receptor mRNA abundance in the ovine fetal kidney. Reproduction 129, 151–159.CrossRefGoogle ScholarPubMed
Budge, H, Bispham, J, Dandrea, J, Evans, E, Heasman, L, Ingleton, PM, Sullivan, C, Wilson, V, Stephenson, T, Symonds, ME 2000. Effect of maternal nutrition on brown adipose tissue and its prolactin receptor status in the fetal lamb. Pediatric Research 47, 781–786.CrossRefGoogle ScholarPubMed
Budge, H, Edwards, LJ, McMillen, IC, Bryce, A, Warnes, K, Pearce, S, 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 71, 359–365.CrossRefGoogle ScholarPubMed
Budge, H, Stephenson, T, Symonds, ME 2007. Maternal nutrient restriction is not equivalent to maternal biological stress. Current Drug Targets 8, 888–893.CrossRefGoogle Scholar
Budge, H, Sebert, S, Sharkey, D, Symonds, ME 2009. Adipose tissue development, nutrition in early life and its impact on later obesity. Proceedings of the Nutrition Society 68, 321–326.CrossRefGoogle ScholarPubMed
Cannon, B, Nedergaard, J 2004. Brown adipose tissue: Function and significance. Physiological Reviews 84, 277–359.CrossRefGoogle ScholarPubMed
Chan, E, Swaminathan, R 1990. Role of prolactin in lactation-induced changes in brown adipose tissue. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 27, R51–R56.CrossRefGoogle Scholar
Chan, LL, Sebert, SP, Hyatt, MA, Stephenson, T, Budge, H, Symonds, ME, Gardner, DS 2009. Effect of maternal nutrient restriction from early to mid gestation on cardiac function and metabolism after adolescent-onset obesity. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 296, R1455–R1463.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 ScholarPubMed
Demas, GE, Bowers, RR, Bartness, TJ, Gettys, TW 2002. Photoperiodic regulation of gene expression in brown and white adipose tissue of Siberian hamsters (phodopus sungorus). American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 282, R114–R121.CrossRefGoogle Scholar
Echtay, KS, Winkler, E, Klingenberg, M 2000. Coenzyme Q is an obligatory cofactor for uncoupling protein function. Nature 408, 609–613.CrossRefGoogle ScholarPubMed
Edwards, LJ, McMillen, IC 2002. Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation. Biology of Reproduction 66, 1562–1569.CrossRefGoogle ScholarPubMed
Enerback, S 2009. The origins of brown adipose tissue. The New England Journal of Medicine 360, 2021–2023.CrossRefGoogle ScholarPubMed
Fowden, AL, Sferruzzi-Perri, AN, Coan, PM, Constancia, M, Burton, GJ 2009. Placental efficiency and adaptation: endocrine regulation. The Journal of Physiology 587, 3459–3472.CrossRefGoogle ScholarPubMed
Freemark, M, Fleenor, D, Driscoll, P, Binart, N, Kelly, P 2001. Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology 142, 532–753.CrossRefGoogle ScholarPubMed
Gardner, DS, Van Bon, BW, Dandrea, J, Goddard, PJ, May, SF, Wilson, V, Stephenson, T, Symonds, ME 2006. Effect of periconceptional undernutrition and gender on hypothalamic-pituitary-adrenal axis function in young adult sheep. Journal of Endocrinology 190, 203–212.CrossRefGoogle ScholarPubMed
Gardner, DS, Buttery, PJ, Daniel, Z, Symonds, ME 2007. Factors affecting birth weight in sheep: maternal environment. Reproduction 133, 297–307.CrossRefGoogle ScholarPubMed
Gluckman, PD, Marti-Henneberg, C, Kaplan, SL, Grumbach, MM 1983. Hormone ontogeny in the ovine fetus: XIV. The effect of 17 beta-estradiol infusion on fetal plasma gonadotropins and prolactin and the maturation of sex steroid-dependent negative feedback. Endocrinology 112, 1618–1623.CrossRefGoogle ScholarPubMed
Gnanalingham, MG, Williams, P, Wilson, V, Bispham, J, Hyatt, MA, Pellicano, A, Budge, H, Stephenson, T, Symonds, ME 2007. Nutritional manipulation between early to mid-gestation: effects on uncoupling protein-2, glucocorticoid sensitivity, IGF-I receptor and cell proliferation but not apoptosis in the ovine placenta. Reproduction 134, 615–623.CrossRefGoogle Scholar
Goldman, BD, Matt, KS, Roychoudhury, P, Stetson, MH 1981. Prolactin release in golden hamsters: photoperiod and gonadal influences. Biology of Reproduction 24, 287–292.CrossRefGoogle ScholarPubMed
Gopalakrishnan, GS, Gardner, DS, Dandrea, J, Langley-Evans, SC, Pearce, S, Kurlak, LO, Walker, RM, Seetho, IW, Keisler, DH, Ramsay, MM, Stephenson, T, Symonds, ME 2005. Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep. British Journal of Nutrition 94, 938–947.CrossRefGoogle ScholarPubMed
Heasman, L, Clarke, L, Firth, K, Stephenson, T, Symonds, ME 1998. Influence of restricted maternal nutrition in early to mid gestation on placental and fetal development at term in sheep. Pediatric Research 44, 546–551.CrossRefGoogle ScholarPubMed
Heijmans, BT, Tobi, EW, Stein, AD, Putter, H, Blauw, GJ, Susser, ES, Slagboom, PE, Lumey, LH 2008. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceedings of the National Academy of Sciences of the United States of America 105, 17046–17049.CrossRefGoogle ScholarPubMed
Heldmaier, G, Steinlechner, S, Rafael, J, Vsiansky, P 1981. Photoperiodic control and effects of melatonin on nonshivering thermogenesis and brown adipose tissue. Science 212, 917–919.CrossRefGoogle ScholarPubMed
Hellmann, JJ, Byers, JE, Bierwagen, BG, Dukes, JS 2008. Five potential consequences of climate change for invasive species. Conservation Biology 22, 534–543.CrossRefGoogle ScholarPubMed
Herrera, E 2002. Implications of dietary fatty acids during pregnancy on placental, fetal and postnatal development – a review. Placenta 23 (suppl. A), S9–S19.CrossRefGoogle ScholarPubMed
Hull, D, Elphick, MC, Broughton, PF 1979. The transfer of fatty acids across the sheep placenta. Journal of Developmental Physiology 1, 31–45.Google Scholar
Hyatt, MA, Keisler, DH, Budge, H, Symonds, ME 2010. Maternal parity and its effect on adipose tissue deposition and endocrine sensitivity in the postnatal sheep. Journal of Endocrinology 204, 173–179.CrossRefGoogle ScholarPubMed
Jaquiery, AL, Oliver, MH, Bloomfield, FH, Connor, KL, Challis, JR, Harding, JE 2006. Fetal exposure to excess glucocorticoid is unlikely to explain the effects of periconceptional undernutrition in sheep. Journal of Physiology 572, 109–118.CrossRefGoogle ScholarPubMed
Klingenspor, M, Klaus, S, Wiesinger, H, Heldmaier, G 1989. Short photoperiod and cold activate brown fat lipoprotein lipase in the Djungarian hamster. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 26, R1123–R1127.CrossRefGoogle Scholar
Lucas, A, Baker, BA, Cole, TJ 1990. Plasma prolactin and clinical outcome in preterm infants. Archives of Diseases in Childhood 65, 977–983.CrossRefGoogle ScholarPubMed
McMillen, IC, Robinson, JS 2005. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiological Reviews 85, 571–633.CrossRefGoogle ScholarPubMed
Murayama, A, Ohmori, K, Fujimura, A, Minami, H, Yasuzawa-Tanaka, K, Kuroda, T, Oie, S, Daitoku, H, Okuwaki, M, Nagata, K, Fukamizu, A, Kimura, K, Shimizu, T, Yanagisawa, J 2008. Epigenetic control of rDNA loci in response to intracellular energy status. Cell 133, 627–639.CrossRefGoogle ScholarPubMed
Nunn, AV, Bell, J, Barter, P 2007. The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance. Nuclear Receptors 5, 1.CrossRefGoogle ScholarPubMed
Ozgul, A, Tuljapurkar, S, Benton, TG, Pemberton, JM, Clutton-Brock, TH, Coulson, T 2009. The dynamics of phenotypic change and the shrinking sheep of St. Kilda. Science 325, 464–467.CrossRefGoogle ScholarPubMed
Park, JH, Stoffers, DA, Nicholls, RD, Simmons, RA 2008. Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. Journal of Clinical Investigation 118, 2316–2423.Google ScholarPubMed
Pearce, S, Budge, H, Mostyn, A, Genever, E, Webb, R, Ingleton, P, Walker, AM, Symonds, ME, Stephenson, T 2005. Prolactin, the prolactin receptor and uncoupling protein abundance and function in adipose tissue during development in young sheep. Journal of Endocrinology 184, 351–359.CrossRefGoogle ScholarPubMed
Power, G 1989. Biology of temperature: the mammalian fetus. Journal of Developmental Physiology 12, 295–304.Google ScholarPubMed
Rathmell, JC, Newgard, CB 2009. Biochemistry. A glucose-to-gene link. Science 324, 1021–1022.CrossRefGoogle ScholarPubMed
Reeves, PG 1997. Components of the AIN-93 diets as improvements in the AIN-76A diet. The Journal of Nutrition 127, 838S–841S.CrossRefGoogle ScholarPubMed
Reynolds, LP, Borowicz, PP, Vonnahme, KA, Johnson, ML, Grazul-Bilska, AT, Wallace, JM, Caton, JS, Redmer, DA 2005. Animal models of placental angiogenesis. Placenta 26, 689–708.CrossRefGoogle ScholarPubMed
Roberts, RM, Smith, GW, Bazer, FW, Cibelli, J, Seidel, GE Jr, Bauman, DE, Reynolds, LP, Ireland, JJ 2009. Research priorities. Farm animal research in crisis. Science 324, 468–469.CrossRefGoogle ScholarPubMed
Schaiff, WT, Barak, Y, Sadovsky, Y 2006. The pleiotropic function of PPAR gamma in the placenta. Molecular and Cellular Endocrinology 249, 10–15.CrossRefGoogle ScholarPubMed
Seale, P, Bjork, B, Yang, W, Kajimura, S, Chin, S, Kuang, S, Scime, A, Devarakonda, S, Conroe, HM, Erdjument-Bromage, H, Tempst, P, Rudnicki, MA, Beier, DR, Spiegelman, BM 2008. PRDM16 controls a brown fat/skeletal muscle switch. Nature 454, 961–967.CrossRefGoogle Scholar
Sebert, SP, Hyatt, MA, Chan, LL, Patel, N, Bell, RC, Keisler, D, Stephenson, T, Budge, H, Symonds, ME, Gardner, DS 2009. Maternal nutrient restriction between early-to-mid gestation and its impact upon appetite regulation following juvenile obesity. Endocrinology 150, 634–641.CrossRefGoogle Scholar
Sharkey, D, Gardner, DS, Fainberg, HP, Wilson, V, Sebert, S, Bos, P, Bell, R, Symonds, ME, Budge, H 2009. Maternal nutrient restriction during pregnancy differentially alters the unfolded protein response in adipose and renal tissue of obese juvenile offspring. The FASEB Journal 23, 1314–1324.CrossRefGoogle ScholarPubMed
Simmons, RA, Flozak, AS, Ogata, ES 1993. The effect of insulin and insulin-like growth factor-I on glucose transport in normal and small for gestational age fetal rats. Endocrinology 133, 1361–1368.CrossRefGoogle ScholarPubMed
Sinclair, KD, Allegrucci, C, Singh, R, Gardner, DS, Sebastian, S, Bispham, J, Thurston, A, Huntley, JF, Rees, WD, Maloney, CA, Lea, RG, Craigon, J, McEvoy, TG, Young, LE 2007. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proceedings of the National Academy of Sciences of the United States of America 104, 19351–19356.CrossRefGoogle ScholarPubMed
Steger, RW, Bartke, A, Goldman, BD, Soares, MJ, Talamantes, F 1983. Effects of short photoperiod on the ability of golden hamster pituitaries to secrete prolactin and gonadotropins in vitro. Biology of Reproduction 29, 872–878.CrossRefGoogle ScholarPubMed
Symonds, ME 2007. Integration of physiological and molecular mechanisms of the developmental origins of adult disease: new concepts and insights. Proceedings of the Nutrition Society 66, 442–450.CrossRefGoogle ScholarPubMed
Symonds, ME, Budge, H 2009. Nutritional models of the developmental programming of adult health and disease. Proceedings of the Nutrition Society 68, 173–178.CrossRefGoogle ScholarPubMed
Symonds, ME, Clarke, L 1996. Nutrition-environment interactions in pregnancy. Nutrition Research Reviews 9, 135–148.CrossRefGoogle ScholarPubMed
Symonds, ME, Lomax, MA 1992. Maternal and environmental influences on thermoregulation in the neonate. Proceedings of the Nutrition Society 51, 165–172.CrossRefGoogle ScholarPubMed
Symonds, ME, Bryant, MJ, Lomax, MA 1986. The effect of shearing on the energy metabolism of the pregnant ewe. British Journal of Nutrition 56, 635–643.CrossRefGoogle ScholarPubMed
Symonds, ME, Bryant, MJ, Lomax, MA 1988. Metabolic adaptation during pregnancy in winter-shorn sheep. Journal of Agricultural Science, Cambridge 111, 137–145.CrossRefGoogle Scholar
Symonds, ME, Bryant, MJ, Lomax, MA 1990. Metabolic adaptation during lactation in winter-shorn sheep. Journal of Agricultural Science 114, 201–205.CrossRefGoogle Scholar
Symonds, ME, Bryant, MJ, Clarke, L, Darby, CJ, Lomax, MA 1992. Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb. Journal of Physiology 455, 487–502.CrossRefGoogle ScholarPubMed
Symonds, ME, Lomax, MA, Kenward, MG, Andrews, DC, Johnson, P 1993. Effect of the prenatal maternal environment on the control of breathing during non-rapid-eye-movement sleep in the developing lamb. Journal of Developmental Physiology 19, 43–50.Google ScholarPubMed
Symonds, ME, Bird, JA, Clarke, L, Gate, JJ, Lomax, MA 1995. Nutrition, temperature and homeostasis during perinatal development. Experimental Physiology 80, 907–940.CrossRefGoogle ScholarPubMed
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, Mostyn, A, Stephenson, T 2001. Cytokines and cytokine-receptors in fetal growth and development. Biochemical Society Transactions 29, 33–37.CrossRefGoogle ScholarPubMed
Symonds, ME, Stephenson, T, Gardner, DS, Budge, H 2007. Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows. Reproduction Fertility and Development 19, 53–63.CrossRefGoogle ScholarPubMed
Symonds, ME, Sebert, SP, Hyatt, MA, Budge, H 2009a. Nutritional programming of the metabolic syndrome. Nature Reviews Endocrinology 5, 604–610.CrossRefGoogle ScholarPubMed
Symonds, ME, Stephenson, T, Budge, H 2009b. Early determinants of cardiovascular disease: the role of early diet in later blood pressure control. The American Journal of Clinical Nutrition 89, 1518S–1522S.CrossRefGoogle ScholarPubMed
Tang, W, Zeve, D, Suh, JM, Bosnakovski, D, Kyba, M, Hammer, RE, Tallquist, MD, Graff, JM 2008. White fat progenitor cells reside in the adipose vasculature. Science 322, 583–586.CrossRefGoogle ScholarPubMed
Timmons, JA, Wennmalm, K, Larsson, O, Walden, TB, Lassmann, T, Petrovic, N, Hamilton, DL, Gimeno, RE, Wahlestedt, C, Baar, K, Nedergaard, J, Cannon, B 2007. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proceedings of the National Academy of Sciences of the United States of America 104, 4401–4406.CrossRefGoogle Scholar
Torres-Farfan, C, Valenzuela, FJ, Mondaca, M, Valenzuela, GJ, Krause, B, Herrera, EA, Riquelme, R, Llanos, AJ, Seron-Ferre, M 2008. Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland. Journal of Physiology 586, 4017–4027.CrossRefGoogle ScholarPubMed
Tseng, YH, Kokkotou, E, Schulz, TJ, Huang, TL, Winnay, JN, Taniguchi, CM, Tran, TT, Suzuki, R, Espinoza, DO, Yamamoto, Y, Ahrens, MJ, Dudley, AT, Norris, AW, Kulkarni, RN, Kahn, CR 2008. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454, 1000–1004.CrossRefGoogle ScholarPubMed
Viengchareun, S, Servel, N, Feve, B, Freemark, M, Lombes, M, Binart, N 2008. Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2. PLoS ONE 3, e1535.CrossRefGoogle ScholarPubMed
Vigas, M, Celko, J, Koska, J 2000. Role of body temperature in exercise-induced growth hormone and prolactin release in non-trained and physically fit subjects. Endocrine Regulation 34, 175–180.Google ScholarPubMed
Virtanen, KA, Lidell, ME, Orava, J, Heglind, M, Westergren, R, Niemi, T, Taittonen, M, Laine, J, Savisto, NJ, Enerback, S, Nuutila, P 2009. Functional brown adipose tissue in healthy adults. The New England Journal of Medicine 360, 1518–1525.CrossRefGoogle ScholarPubMed
Waterland, RA, Jirtle, RL 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Molecular and Cellular Biology 23, 5293–5300.CrossRefGoogle ScholarPubMed
Wellen, KE, Hatzivassiliou, G, Sachdeva, UM, Bui, TV, Cross, JR, Thompson, CB 2009. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324, 1076–1080.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, 11b-hydroxysteroid dehydrogenase isoforms and type 1 angiotensin II receptor in neonatal sheep. Endocrinology 142, 1778–1785.CrossRefGoogle Scholar
Wiesinger, H, Heldmaier, G, Buchberger, A 1989. Effect of photoperiod and acclimation temperature on nonshivering thermogenesis and GDP-binding of brown fat mitochondria in the djungarian hamster phodopus s. Sungorus. Pflugers Arch 413, 667–672.CrossRefGoogle ScholarPubMed
Wigglesworth, JS 1974. Fetal growth retardation. Animal model: uterine vessel ligation in the pregnant rat. American Journal of Pathology 77, 347–350.Google ScholarPubMed
Yiallourides, M, Sebert, SP, Wilson, V, Sharkey, D, Rhind, SM, Symonds, ME, Budge, H 2009. The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-gamma and cell proliferation. Reproduction 138, 601–608.CrossRefGoogle ScholarPubMed