Skip to main content
SpringerLink
Log in
Book cover

Adipose Tissue Biology pp 379–408Cite as

Early Origins of Obesity and Developmental Regulation of Adiposity

  • Chapter
  • First Online:

Abstract

Whilst overweight and obesity result in significant health problems in childhood and adulthood, their origins may lie in earlier life experiences from the nutritional environment of the periconceptional, in utero and postnatal periods. Epidemiological data from human populations, such as from the Dutch “Hunger Winter” studies, show that maternal undernutrition during different phases of pregnancy affects the long-term health of offspring. Importantly, in the context of contemporary populations, maternal overnutrition and obesity also influence offspring health and may induce long-term changes which predispose offspring to insulin resistance, obesity and metabolic syndrome in later life. Although changes in maternal nutrition can alter foetal adiposity without overall changes in birthweight, obese mothers are more likely to have large gestational age babies, and these offspring are more likely to become overweight and obese in later life. In addition to the effects of the maternal nutritional environment, accelerated growth in the early postnatal period, particularly when preceded by foetal growth restriction, can be detrimental to long-term health and increase the risks of obesity and Type 2 diabetes, consequences similar to those following rapid and early increases in BMI in childhood. Key pathways of foetal programming include those mediated through glucocorticoids, with their vital role in developmental regulation of adipose tissue, appetite regulation and energy homeostasis regulated by the hypothalamus, and the neurohormones insulin and leptin influencing the actions of neuropeptides in the hypothalamic nuclei. A better understanding of these processes may provide opportunities for the prevention of obesity and improved public health.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abrams BF, Laros RK Jr (1986) Prepregnancy weight, weight gain, and birth weight. Am J Obstet Gynecol 154:503–509

    PubMed  CAS  Google Scholar 

  • Adair LS, Martorell R, Stein AD, Hallal PC, Sachdev HS, Prabhakaran D, Wills AK, Norris SA, Dahly DL, Lee NR, Victora CG (2009) Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter? Am J Clin Nutr 89:1383–1392

    PubMed  CAS  Google Scholar 

  • Arch JR, Stock MJ, Trayhurn P (1998) Leptin resistance in obese humans: does it exist and what does it mean? Int J Obes Relat Metab Disord 22:1159–1163

    PubMed  CAS  Google Scholar 

  • Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83

    PubMed  CAS  Google Scholar 

  • Armitage JA, Khan IY, Taylor PD, Nathanielsz PW, Poston L (2004) Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol 561:355–377

    PubMed  CAS  Google Scholar 

  • Armitage JA, Poston L, Taylor PD (2008) Developmental origins of obesity and the metabolic syndrome: the role of maternal obesity. Front Horm Res 36:73–84

    PubMed  Google Scholar 

  • Attig L, Solomon G, Ferezou J, Abdennebi-Najar L, Taouis M, Gertler A, Djiane J (2008) Early postnatal leptin blockage leads to a long-term leptin resistance and susceptibility to diet-induced obesity in rats. Int J Obes (Lond) 32:1153–1160

    CAS  Google Scholar 

  • Bamberger CM, Schulte HM, Chrousos GP (1996) Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 17:245–261

    PubMed  CAS  Google Scholar 

  • Barker DJ, Osmond C (1986) Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1:1077–1081

    PubMed  CAS  Google Scholar 

  • Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS (1993) Fetal nutrition and cardiovascular disease in adult life. Lancet 341:938–941

    PubMed  CAS  Google Scholar 

  • Bayol SA, Farrington SJ, Stickland NC (2007) A maternal “junk food” diet in pregnancy and lactation promotes an exacerbated taste for “junk food” and a greater propensity for obesity in rat offspring. Br J Nutr 98:843–851

    PubMed  CAS  Google Scholar 

  • Bayol SA, Macharia R, Farrington SJ, Simbi BH, Stickland NC (2009) Evidence that a maternal “junk food” diet during pregnancy and lactation can reduce muscle force in offspring. Eur J Nutr 48:62–65

    PubMed  Google Scholar 

  • Bieswal F, Ahn MT, Reusens B, Holvoet P, Raes M, Rees WD, Remacle C (2006) The importance of catch-up growth after early malnutrition for the programming of obesity in male rat. Obesity (Silver Spring) 14:1330–1343

    CAS  Google Scholar 

  • Bispham GG, Dandrea J, Wilson V, Budge H, Keisler DH, Broughton PF, 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

    PubMed  CAS  Google Scholar 

  • Bispham J, Gopalakrishnan GS, Dandrea J, Wilson V, Budge H, Keisler DH, Broughton Pipkin 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Boss O, Hagen T, Lowell BB (2000) Uncoupling proteins 2 and 3: potential regulators of mitochondrial energy metabolism. Diabetes 49:143–156

    PubMed  CAS  Google Scholar 

  • Bouret SG (2009) Early life origins of obesity: role of hypothalamic programming. J Pediatr Gastroenterol Nutr 48(Suppl 1):S31–S38

    PubMed  Google Scholar 

  • Bouret SG, Simerly RB (2006) Developmental programming of hypothalamic feeding circuits. Clin Genet 70:295–301

    PubMed  CAS  Google Scholar 

  • Bouret SG, Draper SJ, Simerly RB (2004) Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304:108–110

    PubMed  CAS  Google Scholar 

  • Buckley AJ, Keseru B, Briody J, Thompson M, Ozanne SE, Thompson CH (2005) Altered body composition and metabolism in the male offspring of high fat-fed rats. Metabolism 54:500–507

    PubMed  CAS  Google Scholar 

  • 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. Pediatr Res 47:781–786

    PubMed  CAS  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. J Endocrinol 174:427–433

    PubMed  CAS  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. Pediatr Res 53:302–308

    PubMed  CAS  Google Scholar 

  • 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 messenger RNA abundance in the sheep: differential effects of timing and duration. Biol Reprod 71:359–365

    PubMed  CAS  Google Scholar 

  • Budge H, Gnanalingham MG, Gardner DS, Mostyn A, Stephenson T, Symonds ME (2005) Maternal nutritional programming of fetal adipose tissue development: long-term consequences for later obesity. Birth Defects Res C Embryo Today 75:193–199

    PubMed  CAS  Google Scholar 

  • Caluwaerts S, Lambin S, van Bree R, Peeters H, Vergote I, Verhaeghe J (2007) Diet-induced obesity in gravid rats engenders early hyperadiposity in the offspring. Metabolism 56:1431–1438

    PubMed  CAS  Google Scholar 

  • Casabiell X, Pineiro V, Tome MA, Peino R, Dieguez C, Casanueva FF (1997) Presence of leptin in colostrum and/or breast milk from lactating mothers: a potential role in the regulation of neonatal food intake. J Clin Endocrinol Metab 82:4270–4273

    PubMed  CAS  Google Scholar 

  • Casteilla L, Forest C, Robelin J, Ricquier D, Lombet A, Ailhaud G (1987) Characterization of mitochondrial-uncoupling protein in bovine fetus and newborn calf. Am J Physiol 252:E627–E636

    PubMed  CAS  Google Scholar 

  • Catalano PM (2003) Obesity and pregnancy – the propagation of a viscous cycle? J Clin Endocrinol Metab 88:3505–3506

    PubMed  Google Scholar 

  • Catalano PM, Ehrenberg HM (2006) The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG 113:1126–1133

    PubMed  CAS  Google Scholar 

  • Catalano PM, Drago NM, Amini SB (1995) Maternal carbohydrate metabolism and its relationship to fetal growth and body composition. Am J Obstet Gynecol 172:1464–1470

    PubMed  CAS  Google Scholar 

  • Chakravarthy MV, Booth FW (2004) Eating, exercise, and “thrifty” genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 96:3–10

    PubMed  Google Scholar 

  • Chen H, Simar D, Lambert K, Mercier J, Morris MJ (2008) Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism. Endocrinology 149:5348–5356

    PubMed  CAS  Google Scholar 

  • Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, Dietz PM (2007) Maternal obesity and risk of gestational diabetes mellitus. Diabetes Care 30:2070–2076

    PubMed  Google Scholar 

  • Cianfarani S, Martinez C, Maiorana A, Scire G, Spadoni GL, Boemi S (2004) Adiponectin levels are reduced in children born small for gestational age and are inversely related to postnatal catch-up growth. J Clin Endocrinol Metab 89:1346–1351

    PubMed  CAS  Google 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. Br J Nutr 77:871–883

    PubMed  CAS  Google Scholar 

  • Clarke L, Buss DS, Juniper DT, Lomax MA, Symonds ME (1997b) Adipose tissue development during early postnatal life in ewe-reared lambs. Exp Physiol 82:1015–1027

    PubMed  CAS  Google Scholar 

  • Clarke L, Heasman L, Firth K, Symonds ME (1997c) Influence of route of delivery and ambient temperature on thermoregulation in newborn lambs. Am J Physiol 272:R1931–R1939

    PubMed  CAS  Google Scholar 

  • CMACE (2010) Maternal obesity in the UK: findings from a national project. http://www.oaaanaes.ac.uk/assets/_managed/editor/File/CMACE/CMACE_Obesity_Report_2010_Final%20for%20printing.pdf

  • Cottrell EC, Cripps RL, Duncan JS, Barrett P, Mercer JG, Herwig A, Ozanne SE (2009) Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat. Am J Physiol Regul Integr Comp Physiol 296:R631–R639

    PubMed  CAS  Google Scholar 

  • Curhan GC, Chertow GM, Willett WC, Spiegelman D, Colditz GA, Manson JE, Speizer FE, Stampfer MJ (1996) Birth weight and adult hypertension and obesity in women. Circulation 94:1310–1315

    PubMed  CAS  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 (GLUT-1) abundance in sheep. Reproduction 122:793–800

    PubMed  CAS  Google Scholar 

  • Desai M, Gayle D, Han G, Ross MG (2007) Programmed hyperphagia due to reduced anorexigenic mechanisms in intrauterine growth-restricted offspring. Reprod Sci 14:329–337

    PubMed  Google Scholar 

  • Devaskar SU, Ollesch C, Rajakumar RA, Rajakumar PA (1997) Developmental changes in ob gene expression and circulating leptin peptide concentrations. Biochem Biophys Res Commun 238:44–47

    PubMed  CAS  Google Scholar 

  • Dorner G, Plagemann A (1994) Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life. Horm Metab Res 26:213–221

    PubMed  CAS  Google Scholar 

  • Edington J (1999) Problems of nutritional assessment in the community. Proc Nutr Soc 58:47–51

    PubMed  CAS  Google Scholar 

  • Edwards LJ, McMillen IC (2001) Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol 533:561–570

    PubMed  CAS  Google Scholar 

  • Elmquist JK, Elias CF, Saper CB (1999) From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 22:221–232

    PubMed  CAS  Google Scholar 

  • Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Heintze U, Janke J, Luft FC, Sharma AM (2004) Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss. Obes Res 12:9–17

    PubMed  CAS  Google Scholar 

  • Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond C, Barker DJ (1999) Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ 318:427–431

    PubMed  CAS  Google Scholar 

  • Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJ (2003) Early adiposity rebound in childhood and risk of Type 2 diabetes in adult life. Diabetologia 46:190–194

    PubMed  CAS  Google Scholar 

  • Fall CH, Osmond C, Barker DJ, Clark PM, Hales CN, Stirling Y, Meade TW (1995) Fetal and infant growth and cardiovascular risk factors in women. BMJ 310:428–432

    PubMed  CAS  Google Scholar 

  • Festing MF (2006) Design and statistical methods in studies using animal models of development. ILAR J 47:5–14

    PubMed  CAS  Google Scholar 

  • Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin MF, Surwit RS, Ricquier D, Warden CH (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15:269–272

    PubMed  CAS  Google Scholar 

  • Forsdahl A (1977) Are poor living conditions in childhood and adolescence an important risk factor for arteriosclerotic heart disease? Br J Prev Soc Med 31:91–95

    PubMed  CAS  Google Scholar 

  • Fowden AL, Li J, Forhead AJ (1998) Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance? Proc Nutr Soc 57:113–122

    PubMed  CAS  Google Scholar 

  • Franke K, Harder T, Aerts L, Melchior K, Fahrenkrog S, Rodekamp E, Ziska T, van Assche FA, Dudenhausen JW, Plagemann A (2005) “Programming” of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats. Brain Res 1031:276–283

    PubMed  CAS  Google Scholar 

  • Gaillard D, Wabitsch M, Pipy B, Negrel R (1991) Control of terminal differentiation of adipose precursor cells by glucocorticoids. J Lipid Res 32:569–579

    PubMed  CAS  Google Scholar 

  • Gardner DS, Pearce S, Dandrea J, Walker R, Ramsay MM, Stephenson T, Symonds ME (2004) Peri-implantation undernutrition programs blunted angiotensin II evoked baroreflex responses in young adult sheep. Hypertension 43:1290–1296

    PubMed  CAS  Google Scholar 

  • Gardner DS, Tingey K, van Bon BW, Ozanne SE, Wilson V, Dandrea J, Keisler DH, Stephenson T, Symonds ME (2005) Programming of glucose-insulin metabolism in adult sheep after maternal undernutrition. Am J Physiol Regul Integr Comp Physiol 289:R947–R954

    PubMed  CAS  Google Scholar 

  • 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. J Endocrinol 190:203–212

    PubMed  CAS  Google Scholar 

  • Gluckman PD, Hanson MA (2004) Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res 56:311–317

    PubMed  Google Scholar 

  • Gluckman PD, Hanson MA, Spencer HG (2005) Predictive adaptive responses and human evolution. Trends Ecol Evol 20:527–533

    PubMed  Google Scholar 

  • Gnanalingham MG, Mostyn A, Symonds ME, Stephenson T (2005) Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2. Am J Physiol Regul Integr Comp Physiol 289:R1407–R1415

    PubMed  CAS  Google Scholar 

  • Gopalakrishnan RS, Stephenson T, Kyle CE, Brooks AN, Rae MT, Symonds ME (2001) Effects of maternal nutrient restriction at defined periods in early to mid gestation on placento-fetal, kidney and adipose tissue weights at 110days gestation in sheep. Early Hum Dev 63:58–59

    Google Scholar 

  • Gorski JN, Dunn-Meynell AA, Hartman TG, Levin BE (2006) Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance. Am J Physiol Regul Integr Comp Physiol 291:R768–R778

    PubMed  CAS  Google Scholar 

  • Grayson BE, Allen SE, Billes SK, Williams SM, Smith MS, Grove KL (2006) Prenatal development of hypothalamic neuropeptide systems in the nonhuman primate. Neuroscience 143:975–986

    PubMed  CAS  Google Scholar 

  • Grimaldi PA (2001) The roles of PPARs in adipocyte differentiation. Prog Lipid Res 40:269–281

    PubMed  CAS  Google Scholar 

  • Grove KL, Grayson BE, Glavas MM, Xiao XQ, Smith MS (2005) Development of metabolic systems. Physiol Behav 86:646–660

    PubMed  CAS  Google Scholar 

  • Guo F, Jen KL (1995) High-fat feeding during pregnancy and lactation affects offspring metabolism in rats. Physiol Behav 57:681–686

    PubMed  CAS  Google Scholar 

  • Hales CN, Barker DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60:5–20

    PubMed  CAS  Google Scholar 

  • Howie GJ, Sloboda DM, Kamal T, Vickers MH (2009) Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol 587:905–915

    PubMed  CAS  Google Scholar 

  • Huxley RR, Shiell AW, Law CM (2000) The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 18:815–831

    PubMed  CAS  Google Scholar 

  • Ibanez L, Ong K, Dunger DB, de Zegher F (2006) Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. J Clin Endocrinol Metab 91:2153–2158

    PubMed  CAS  Google Scholar 

  • Ibanez L, Suarez L, Lopez-Bermejo A, Diaz M, Valls C, de Zegher F (2008) Early development of visceral fat excess after spontaneous catch-up growth in children with low birth weight. J Clin Endocrinol Metab 93:925–928

    PubMed  CAS  Google Scholar 

  • Jaquet D, Leger J, Tabone MD, Czernichow P, Levy-Marchal C (1999) High serum leptin concentrations during catch-up growth of children born with intrauterine growth retardation. J Clin Endocrinol Metab 84:1949–1953

    PubMed  CAS  Google Scholar 

  • Khan IY, Taylor PD, Dekou V, Seed PT, Lakasing L, Graham D, Dominiczak AF, Hanson MA, Poston L (2003) Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension 41:168–175

    PubMed  CAS  Google Scholar 

  • Kiel DW, Dodson EA, Artal R, Boehmer TK, Leet TL (2007) Gestational weight gain and pregnancy outcomes in obese women: how much is enough? Obstet Gynecol 110:752–758

    PubMed  Google Scholar 

  • Kim SY, Dietz PM, England L, Morrow B, Callaghan WM (2007) Trends in pre-pregnancy obesity in nine states, 1993–2003. Obesity (Silver Spring) 15:986–993

    Google Scholar 

  • Korotkova M, Gabrielsson B, Hanson LA, Strandvik B (2001) Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups. J Lipid Res 42:359–365

    PubMed  CAS  Google Scholar 

  • Kotelevtsev Y, Holmes MC, Burchell A, Houston PM, Schmoll D, Jamieson P, Best R, Brown R, Edwards CR, Seckl JR, Mullins JJ (1997) 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc Natl Acad Sci USA 94:14924–14929

    PubMed  CAS  Google Scholar 

  • Kozak R, Burlet A, Burlet C, Beck B (2000) Dietary composition during fetal and neonatal life affects neuropeptide Y functioning in adult offspring. Brain Res Dev Brain Res 125:75–82

    PubMed  CAS  Google Scholar 

  • Law CM, Barker DJ, Osmond C, Fall CH, Simmonds SJ (1992) Early growth and abdominal fatness in adult life. J Epidemiol Community Health 46:184–186

    PubMed  CAS  Google Scholar 

  • Levin BE (2006) Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis. Philos Trans R Soc Lond B Biol Sci 361:1107–1121

    PubMed  CAS  Google Scholar 

  • Levine JA, Lanningham-Foster LM, McCrady SK, Krizan AC, Olson LR, Kane PH, Jensen MD, Clark MM (2005) Interindividual variation in posture allocation: possible role in human obesity. Science 307:584–586

    PubMed  CAS  Google Scholar 

  • Lucas A (1991) Programming by early nutrition in man. Ciba Found Symp 156:38–50; discussion 50–55

    Google Scholar 

  • Mantzoros CS, Flier JS (2000) Editorial: leptin as a therapeutic agent – trials and tribulations. J Clin Endocrinol Metab 85:4000–4002

    PubMed  CAS  Google Scholar 

  • Martinez JA (2000) Body-weight regulation: causes of obesity. Proc Nutr Soc 59:337–345

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • McCance RA, Widdowson EM (1974) The determinants of growth and form. Proc R Soc Lond B Biol Sci 185:1–17

    PubMed  CAS  Google Scholar 

  • McMillen IC, Adam CL, Muhlhausler BS (2005) Early origins of obesity: programming the appetite regulatory system. J Physiol 565:9–17

    PubMed  CAS  Google Scholar 

  • Morris MJ, Chen H (2009) Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth. Int J Obes (Lond) 33:115–122

    CAS  Google Scholar 

  • Morrison JL, Duffield JA, Muhlhausler BS, Gentili S, McMillen IC (2010) Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity. Pediatr Nephrol 25:669–677

    PubMed  Google Scholar 

  • Muhlhausler BS, Roberts CT, Yuen BS, Marrocco E, Budge H, Symonds ME, McFarlane JR, Kauter KG, Stagg P, Pearse JK, McMillen IC (2003) Determinants of fetal leptin synthesis, fat mass, and circulating leptin concentrations in well-nourished ewes in late pregnancy. Endocrinology 144:4947–4954

    PubMed  CAS  Google Scholar 

  • Muhlhausler BS, McMillen IC, Rouzaud G, Findlay PA, Marrocco EM, Rhind SM, Adam CL (2004) Appetite regulatory neuropeptides are expressed in the sheep hypothalamus before birth. J Neuroendocrinol 16:502–507

    PubMed  CAS  Google Scholar 

  • Muhlhausler BS, Adam CL, Marrocco EM, Findlay PA, Roberts CT, McFarlane JR, Kauter KG, McMillen IC (2005) Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation. J Physiol 565:185–195

    PubMed  CAS  Google Scholar 

  • Muhlhausler BS, Adam CL, Findlay PA, Duffield JA, McMillen IC (2006) Increased maternal nutrition alters development of the appetite-regulating network in the brain. FASEB J 20:1257–1259

    PubMed  CAS  Google Scholar 

  • Muhlhausler BS, Duffield JA, McMillen IC (2007) Increased maternal nutrition stimulates peroxisome proliferator activated receptor-gamma, adiponectin, and leptin messenger ribonucleic acid expression in adipose tissue before birth. Endocrinology 148:878–885

    PubMed  CAS  Google Scholar 

  • Muhlhausler BS, Duffield JA, Ozanne SE, Pilgrim C, Turner N, Morrison JL, McMillen IC (2009) The transition from fetal growth restriction to accelerated postnatal growth: a potential role for insulin signalling in skeletal muscle. J Physiol 587:4199–4211

    PubMed  CAS  Google Scholar 

  • Oliver P, Pico C, de Matteis R, Cinti S, Palou A (2002) Perinatal expression of leptin in rat stomach. Dev Dyn 223:148–154

    PubMed  CAS  Google Scholar 

  • Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB (2000) Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ 320:967–971

    PubMed  CAS  Google Scholar 

  • Ozanne SE, Hales CN (2004) Catch-up growth and obesity in male mice. Nature 427:411–412

    PubMed  CAS  Google Scholar 

  • Phillips DI, Fall CH, Cooper C, Norman RJ, Robinson JS, Owens PC (1999) Size at birth and plasma leptin concentrations in adult life. Int J Obes Relat Metab Disord 23:1025–1029

    PubMed  CAS  Google Scholar 

  • Phillips ID, Anthony RV, Simonetta G, Owens JA, Robinson JS, McMillen IC (2001) Restriction of fetal growth has a differential impact on fetal prolactin and prolactin receptor mRNA expression. J Neuroendocrinol 13:175–181

    PubMed  CAS  Google Scholar 

  • Plagemann A, Harder T, Rake A, Melchior K, Rittel F, Rohde W, Dorner G (1998) Hypothalamic insulin and neuropeptide Y in the offspring of gestational diabetic mother rats. Neuroreport 9:4069–4073

    PubMed  CAS  Google Scholar 

  • Plagemann A, Harder T, Janert U, Rake A, Rittel F, Rohde W, Dorner G (1999) Malformations of hypothalamic nuclei in hyperinsulinemic offspring of rats with gestational diabetes. Dev Neurosci 21:58–67

    PubMed  CAS  Google Scholar 

  • Power GG (1989) Biology of temperature: the mammalian fetus. J Dev Physiol 12:295–304

    PubMed  CAS  Google Scholar 

  • Prokopec M, Bellisle F (1993) Adiposity in Czech children followed from 1 month of age to adulthood: analysis of individual BMI patterns. Ann Hum Biol 20:517–525

    PubMed  CAS  Google Scholar 

  • Proulx K, Richard D, Walker CD (2002) Leptin regulates appetite-related neuropeptides in the hypothalamus of developing rats without affecting food intake. Endocrinology 143:4683–4692

    PubMed  CAS  Google Scholar 

  • Rattanatray L, Maclaughlin SM, Kleemann DO, Walker SK, Muhlhausler BS, McMillen IC (2010) Impact of maternal periconceptional overnutrition on fat mass and expression of adipogenic and lipogenic genes in visceral and subcutaneous fat depots in the postnatal lamb. Endocrinology 151:5195–5205

    PubMed  CAS  Google Scholar 

  • Ravelli AC, van der Meulen JH, Osmond C, Barker DJ, Bleker OP (1999) Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 70:811–816

    PubMed  CAS  Google Scholar 

  • Reddy JK, Hashimoto T (2001) Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system. Annu Rev Nutr 21:193–230

    PubMed  CAS  Google Scholar 

  • Retnakaran R, Hanley AJ, Raif N, Connelly PW, Sermer M, Zinman B (2003) C-reactive protein and gestational diabetes: the central role of maternal obesity. J Clin Endocrinol Metab 88:3507–3512

    PubMed  CAS  Google Scholar 

  • Rolland-Cachera MF, Deheeger M, Bellisle F, Sempe M, Guilloud-Bataille M, Patois E (1984) Adiposity rebound in children: a simple indicator for predicting obesity. Am J Clin Nutr 39:129–135

    PubMed  CAS  Google Scholar 

  • Rolland-Cachera MF, Deheeger M, Guilloud-Bataille M, Avons P, Patois E, Sempe M (1987) Tracking the development of adiposity from one month of age to adulthood. Ann Hum Biol 14:219–229

    PubMed  CAS  Google Scholar 

  • Rolland-Cachera MF, Deheeger M, Maillot M, Bellisle F (2006) Early adiposity rebound: causes and consequences for obesity in children and adults. Int J Obes (Lond) 30(Suppl 4):S11–S17

    Google Scholar 

  • Roseboom TJ, van der Meulen JH, Osmond C, Barker DJ, Ravelli AC, Bleker OP (2000a) Plasma lipid profiles in adults after prenatal exposure to the Dutch famine. Am J Clin Nutr 72:1101–1106

    PubMed  CAS  Google Scholar 

  • Roseboom TJ, van der Meulen JH, Osmond C, Barker DJ, Ravelli AC, Schroeder-Tanka JM, van Montfrans GA, Michels RP, Bleker OP (2000b) Coronary heart disease after prenatal exposure to the Dutch famine, 1944–45. Heart 84:595–598

    PubMed  CAS  Google Scholar 

  • Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP (2001) Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 185:93–98

    PubMed  CAS  Google Scholar 

  • Royster M, Driscoll P, Kelly PA, Freemark M (1995) The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand-binding activity and induction of expression in late gestation. Endocrinology 136:3892–3900

    PubMed  CAS  Google Scholar 

  • Sayer AA, Syddall HE, Dennison EM, Gilbody HJ, Duggleby SL, Cooper C, Barker DJ, Phillips DI (2004) Birth weight, weight at 1 y of age, and body composition in older men: findings from the Hertfordshire Cohort Study. Am J Clin Nutr 80:199–203

    PubMed  CAS  Google Scholar 

  • Schwartz MW (2001) Brain pathways controlling food intake and body weight. Exp Biol Med (Maywood) 226:978–981

    CAS  Google Scholar 

  • Shankar K, Harrell A, Liu X, Gilchrist JM, Ronis MJ, Badger TM (2008) Maternal obesity at conception programs obesity in the offspring. Am J Physiol Regul Integr Comp Physiol 294:R528–R538

    PubMed  CAS  Google Scholar 

  • Shelley P, Martin-Gronert MS, Rowlerson A, Poston L, Heales SJ, Hargreaves IP, McConnell JM, Ozanne SE, Fernandez-Twinn DS (2009) Altered skeletal muscle insulin signaling and mitochondrial complex II-III linked activity in adult offspring of obese mice. Am J Physiol Regul Integr Comp Physiol 297:R675–R681

    PubMed  CAS  Google Scholar 

  • Siervogel RM, Roche AF, Guo SM, Mukherjee D, Chumlea WC (1991) Patterns of change in weight/stature2 from 2 to 18 years: findings from long-term serial data for children in the Fels longitudinal growth study. Int J Obes 15:479–485

    PubMed  CAS  Google Scholar 

  • Singh BS, Westfall TC, Devaskar SU (1997) Maternal diabetes-induced hyperglycemia and acute intracerebral hyperinsulinism suppress fetal brain neuropeptide Y concentrations. Endocrinology 138:963–969

    PubMed  CAS  Google Scholar 

  • Singhal A, Farooqi IS, O’Rahilly S, Cole TJ, Fewtrell M, Lucas A (2002) Early nutrition and leptin concentrations in later life. Am J Clin Nutr 75:993–999

    PubMed  CAS  Google Scholar 

  • Soto N, Bazaes RA, Pena V, Salazar T, Avila A, Iniguez G, Ong KK, Dunger DB, Mericq MV (2003) Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort. J Clin Endocrinol Metab 88:3645–3650

    PubMed  CAS  Google Scholar 

  • Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228

    PubMed  CAS  Google Scholar 

  • Stephenson T, Budge H, Mostyn A, Pearce S, Webb R, Symonds ME (2001) Fetal and neonatal adipose maturation: a primary site of cytokine and cytokine-receptor action. Biochem Soc Trans 29:80–85

    PubMed  CAS  Google Scholar 

  • Stewart PM, Krozowski ZS (1999) 11 beta-Hydroxysteroid dehydrogenase. Vitam Horm 57:249–324

    PubMed  CAS  Google Scholar 

  • Symonds ME, Lomax MA (1992) Maternal and environmental influences on thermoregulation in the neonate. Proc Nutr Soc 51:165–172

    PubMed  CAS  Google Scholar 

  • Symonds ME, Phillips ID, Anthony RV, Owens JA, McMillen IC (1998) Prolactin receptor gene expression and foetal adipose tissue. J Neuroendocrinol 10:885–890

    PubMed  CAS  Google Scholar 

  • Symonds ME, Budge H, Stephenson T (2000) Limitations of models used to examine the influence of nutrition during pregnancy and adult disease. Arch Dis Child 83:215–219

    PubMed  CAS  Google Scholar 

  • Symonds ME, Mostyn A, Pearce S, Budge H, Stephenson T (2003) Endocrine and nutritional regulation of fetal adipose tissue development. J Endocrinol 179:293–299

    PubMed  CAS  Google Scholar 

  • Symonds ME, Pearce S, Bispham J, Gardner DS, Stephenson T (2004) Timing of nutrient restriction and programming of fetal adipose tissue development. Proc Nutr Soc 63:397–403

    PubMed  Google Scholar 

  • Symonds ME, Stephenson T, Gardner DS, Budge H (2007) Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows. Reprod Fertil Dev 19:53–63

    PubMed  Google Scholar 

  • Taylor PD, Poston L (2007) Developmental programming of obesity in mammals. Exp Physiol 92:287–298

    PubMed  CAS  Google Scholar 

  • Taylor RW, Goulding A, Lewis-Barned NJ, Williams SM (2004) Rate of fat gain is faster in girls undergoing early adiposity rebound. Obes Res 12:1228–1230

    PubMed  Google Scholar 

  • Taylor PD, McConnell J, Khan IY, Holemans K, Lawrence KM, Asare-Anane H, Persaud SJ, Jones PM, Petrie L, Hanson MA, Poston L (2005) Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol 288:R134–R139

    PubMed  CAS  Google Scholar 

  • Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD (2000) Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab 279:E83–E87

    PubMed  CAS  Google Scholar 

  • Vickers MH, Breier BH, McCarthy D, Gluckman PD (2003) Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. Am J Physiol Regul Integr Comp Physiol 285:R271–R273

    PubMed  CAS  Google Scholar 

  • Vickers MH, Gluckman PD, Coveny AH, Hofman PL, Cutfield WS, Gertler A, Breier BH, Harris M (2005) Neonatal leptin treatment reverses developmental programming. Endocrinology 146:4211–4216

    PubMed  CAS  Google Scholar 

  • Vieau D, Sebaai N, Leonhardt M, Dutriez-Casteloot I, Molendi-Coste O, Laborie C, Breton C, Deloof S, Lesage J (2007) HPA axis programming by maternal undernutrition in the male rat offspring. Psychoneuroendocrinology 32(Suppl 1):S16–S20

    PubMed  CAS  Google Scholar 

  • Visscher TL, Seidell JC (2001) The public health impact of obesity. Annu Rev Public Health 22:355–375

    PubMed  CAS  Google Scholar 

  • Wallace JM, Milne JS, Aitken RP (2010) Effect of weight and adiposity at conception and wide variations in gestational dietary intake on pregnancy outcome and early postnatal performance in young adolescent sheep. Biol Reprod 82:320–330

    PubMed  CAS  Google Scholar 

  • Warnes KE, Morris MJ, Symonds ME, Phillips ID, Clarke IJ, Owens JA, McMillen IC (1998) Effects of increasing gestation, cortisol and maternal undernutrition on hypothalamic neuropeptide Y expression in the sheep fetus. J Neuroendocrinol 10:51–57

    PubMed  CAS  Google Scholar 

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    PubMed  CAS  Google Scholar 

  • Whitaker RC (2004) Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics 114:e29–e36

    PubMed  Google Scholar 

  • Whitaker RC, Pepe MS, Wright JA, Seidel KD, Dietz WH (1998) Early adiposity rebound and the risk of adult obesity. Pediatrics 101:E5

    PubMed  CAS  Google Scholar 

  • Whorwood CB, Firth KM, Budge H, Symonds ME (2001) Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11beta-hydroxysteroid dehydrogenase isoforms, and type 1 angiotensin ii receptor in neonatal sheep. Endocrinology 142:2854–2864

    PubMed  CAS  Google Scholar 

  • Williams S, Davie G, Lam F (1999) Predicting BMI in young adults from childhood data using two approaches to modelling adiposity rebound. Int J Obes Relat Metab Disord 23:348–354

    PubMed  CAS  Google Scholar 

  • Williams PJ, Kurlak LO, Perkins AC, Budge H, Stephenson T, Keisler D, Symonds ME, Gardner DS (2007) Hypertension and impaired renal function accompany juvenile obesity: the effect of prenatal diet. Kidney Int 72:279–289

    PubMed  CAS  Google Scholar 

  • Yajnik CS (2004) Obesity epidemic in India: intrauterine origins? Proc Nutr Soc 63:387–396

    PubMed  CAS  Google Scholar 

  • Yan X, Zhu MJ, Xu W, Tong JF, Ford SP, Nathanielsz PW, Du M (2010) Up-regulation of Toll-like receptor 4/nuclear factor-kappaB signaling is associated with enhanced adipogenesis and insulin resistance in fetal skeletal muscle of obese sheep at late gestation. Endocrinology 151:380–387

    PubMed  CAS  Google Scholar 

  • Yu CK, Teoh TG, Robinson S (2006) Obesity in pregnancy. BJOG 113:1117–1125

    PubMed  CAS  Google Scholar 

  • Yuen BS, McMillen IC, Symonds ME, Owens PC (1999) Abundance of leptin mRNA in fetal adipose tissue is related to fetal body weight. J Endocrinol 163:R11–R14

    PubMed  CAS  Google Scholar 

  • 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 J 17:1102–1104

    PubMed  CAS  Google Scholar 

  • Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y, Fujii S (2005) Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab 1:371–378

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Academic Division of Child Health, School of Clinical Sciences, Queen’s Medical Centre, University of Nottingham, E Floor, East Block, Nottingham, NG7 2UH, UK

    Shalini Ojha & Helen Budge

Authors
  1. Shalini Ojha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helen Budge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helen Budge .

Editor information

Editors and Affiliations

  1. Queen's Medical Centre, School of Human Development, University Hospital, Nottingham, NG7 2UH, United Kingdom

    Michael E. Symonds

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Ojha, S., Budge, H. (2012). Early Origins of Obesity and Developmental Regulation of Adiposity. In: Symonds, M. (eds) Adipose Tissue Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0965-6_11

Download citation

Publish with us

Policies and ethics

Search

Navigation