Skip to main content Accessibility help
  • Print publication year: 2012
  • Online publication date: August 2012

12 - Adipose tissue development and its potential contribution to later obesity

from Section 3 - Long-term consequences


The early life environment may persistently influence the development of adipose tissue, thereby predisposing the offspring to obesity. This chapter reviews the limited information available, which suggests that the early life nutritional environment can influence adipocyte biology and influence the risk of obesity in later life. The maternal nutritional environment can have a major impact on long-term metabolic health of the offspring. More information from animal models is available in relation to the influence of maternal nutrient restriction in early and mid-gestation in sheep, which also increases glucocorticoid receptor and 11ßHSD1 expression and reduces expression of 11ßHSD2 in ovine perirenal adipose tissue at term, changes that persist up to six months of age. Both animal experiments and human epidemiological data suggest that there is a substantial role for early life experiences in the programming of adipose tissue function and distribution.

Related content

Powered by UNSILO
Sebert, S P Hyatt, M A Chan, L L Maternal nutrient restriction between early and midgestation and its impact upon appetite regulation after juvenile obesity Endocrinology 2009 150 634
Symonds, M E Budge, H. Nutritional models of the developmental programming of adult health and disease Proc Nutr Soc 2009 68 173
Budge, H Symonds, M E Kurjak, A Chervenak, FA Textbook of Perinatal Medicine CRC Press Boca Raton 2006
Cannon, B Nedergaard, J. Developmental biology: neither fat nor flesh Nature 2008 454 947
Cypess, A M Kahn, C R The role and importance of brown adipose tissue in energy homeostasis Curr Opin Pediatr 2010 22 478
Cypess, A M Kahn, C R Brown fat as a therapy for obesity and diabetes Curr Opin Endocrinol Diabetes Obes 2010 17 143
Power, G. Biology of temperature: the mammalian fetus J Dev Physiol 1989 12 295
Symonds, M E Budge, H Perkins, A C Adipose tissue development – impact of the early life environment Prog Biophys Mol Biol 2011 106 300
Symonds, M E Lomax, M A Maternal and environmental influences on thermoregulation in the neonate Proc Nutr Soc 1992 51 165
Seale, P Kajimura, S Spiegelman, B M Transcriptional control of brown adipocyte development and physiological function – of mice and men Genes Dev 2009 23 788
Rothwell, N J Stock, M J A role for brown adipose tissue in diet-induced thermogenesis Nature 1979 281 31
Rothwell, N J Stock, M J Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour Clin Sci (Lond) 1983 64 19
Symonds, M E Stephenson, T Gardner, D S Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows Reprod Fertil Dev 2007 19 53
Cannon, B Connoley, E Obregon, M-J Kunzel, W A (e, Jesen The Endocrine Control of the Fetus Berlin Springer Verlag 1988
Symonds, M E Mostyn, A Pearce, S Endocrine and nutritional regulation of fetal adipose tissue development J Endocrinol 2003 179 293
Bispham, J Gopalakrishnan, G S Dandrea, J Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development Endocrinology 2003 144 3575
Symonds, M E Sebert, S P Budge, H. The impact of diet during early life and its contribution to later disease: critical checkpoints in development and their long-term consequences for metabolic health Proc Nutr Soc 2009 68 416
HAPO Study Cooperative Research Group Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics Diabetes 2009 58 453
McMillen, I C Robinson, J S Developmental origins of the metabolic syndrome: prediction, plasticity, and programming Physiol Rev 2005 85 571
Roseboom, T J van der Meulen, J H Ravelli, A C Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview Twin Res 2001 4 293
Centre for Maternal and Child Enquiries (CMACE) 2010
Budge, H Bispham, J Dandrea, J Effect of maternal nutrition on brown adipose tissue and prolactin receptor status in the fetal lamb Pediatr Res 2000 47 781
Gnanalingham, M G Mostyn, A Symonds, M E Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2 Am J Physiol Regul Integr Comp Physiol 2005 289 R1407
Tang, W Zeve, D Suh, J M White fat progenitor cells reside in the adipose vasculature Science 2008 322 583
Spalding, K L Arner, E Westermark, P O Dynamics of fat cell turnover in humans Nature 2008 453 783
Symonds, M E Mostyn, A Stephenson, T. Cytokines and cytokine-receptors in fetal growth and development Biochem Soc Trans 2001 29 33
Budge, H Dandrea, J Mostyn, A 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 2003 53 302
Clarke, L Buss, D S Juniper, D T Adipose tissue development during early postnatal life in ewe-reared lambs Exp Physiol 1997 82 1015
Lean, M E Brown adipose tissue in humans Proc Nutr Soc 1989 48 243
Seale, P Bjork, B Yang, W PRDM16 controls a brown fat/skeletal muscle switch Nature 2008 454 961
Gilsanz, V Chung, S A Jackson, H Functional brown adipose tissue is related to muscle volume in children and adolescents J Pediatr 2011 158 722
Yuen, B S Owens, P C Muhlhausler, B S Leptin alters the structural and functional characteristics of adipose tissue before birth FASEB J 2003 17 1102
Symonds, M E Pearce, S Bispham, J Timing of nutrient restriction and programming of fetal adipose tissue development Proc Nutr Soc 2004 63 397
Lomax, M A Sadiq, F Karamanlidis, G Ontogenic loss of brown adipose tissue sensitivity to beta-adrenergic stimulation in the ovine Endocrinology 2007 148 461
Sharkey, D Symonds, M E Budge, H. Adipose tissue inflammation: developmental ontogeny and consequences of gestational nutrient restriction in offspring Endocrinology 2009 150 3913
Mostyn, A Wilson, V Dandrea, J Ontogeny and nutritional manipulation of mitochondrial protein abundance in adipose tissue and the lungs of postnatal sheep Br J Nutr 2003 90 323
Stewart, F M Freeman, D J Ramsay, J E Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers J Clin Endocrinol Metab 2007 92 969
Sullivan, E L Smith, M S Grove, K L Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood Neuroendocrinology 2011 93 1
Bamberger, C M Schulte, H M Chrousos, G P Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids Endocr Rev 1996 17 245
Stewart, P M Krozowski, Z S 11 beta-Hydroxysteroid dehydrogenase Vitam Horm 1999 57 249
Gnanalingham, M G Mostyn, A Dandrea, J Ontogeny and nutritional programming of uncoupling protein-2 (UCP2) and glucocorticoid receptor (GCR) mRNA in the ovine lung J Physiol 2005 565 159
Sebert, S P Dellschaft, N S Chan, L L Maternal nutrient restriction during late gestation and early postnatal growth in sheep differentially reset the control of energy metabolism in the gastric mucosa Endocrinology 2011 152 2816
Engeli, S Bohnke, J Feldpausch, M Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss Obes Res 2004 12 9
Paulmyer-Lacroix, O Boullu, S Oliver, C Expression of the mRNA coding for 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue from obese patients: an in situ hybridization study J Clin Endocrinol Metab 2002 87 2701
Taylor, P D Khan, I Y Lakasing, L Uterine artery function in pregnant rats fed a diet supplemented with animal lard Exp Physiol 2003 88 389
Grayson, B E Kievit, P Smith, M S Critical determinants of hypothalamic appetitive neuropeptide development and expression: species considerations Front Neuroendocrinol 2010 31 16
Clarke, L Heasman, L Symonds, M E Influence of maternal dexamethasone administration on thermoregulation in lambs delivered by caesarean section J Endocrinol 1998 156 307
Gnanalingham, M Hyatt, M Bispham, J Maternal dexamethasone administration and the maturation of perirenal adipose tissue of the neonatal sheep Organogenesis 2008 4 188
Bouret, S G Early life origins of obesity: role of hypothalamic programming J Pediatr Gastroenterol Nutr 2009 48( S31
Gorski, J N Dunn-Meynell, A A Levin, B E Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats Am J Physiol Regul Integr Comp Physiol 2007 292 R1782
Kirk, S L Samuelsson, A M Argenton, M Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring PLoS One 2009 4 e5870
Ferezou-Viala, J Roy, A F Serougne, C Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring Am J Physiol Regul Integr Comp Physiol 2007 293 R1056
Ainge, H Thompson, C Ozanne, S E A systematic review on animal models of maternal high fat feeding and offspring glycaemic control Int J Obes (Lond) 2011 35 325
McMillen, I C Adam, C L Muhlhausler, B S Early origins of obesity: programming the appetite regulatory system J Physiol 2005 565 9
Reddy, J K Hashimoto, T. Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system Annu Rev Nutr 2001 21 193
Altiok, S Xu, M Spiegelman, B M PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A Genes Dev 1997 11 1987
Fasshauer, M Klein, J Kriauciunas, K M Essential role of insulin receptor substrate 1 in differentiation of brown adipocytes Mol Cell Biol 2001 21 319
Miki, H Yamauchi, T Suzuki, R Essential role of insulin receptor substrate 1 (IRS-1) and IRS-2 in adipocyte differentiation Mol Cell Biol 2001 21 2521
Symonds, M E Sebert, S Budge, H. The obesity epidemic: from the environment to epigenetics – not simply a response to dietary manipulation in a thermoneutral environment Frontiers in Epigenomics 2011 2
Minge, C E Bennett, B D Norman, R J Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality Endocrinology 2008 149 2646
Shankar, K Harrell, A Liu, X Maternal obesity at conception programs obesity in the offspring Am J Physiol Regul Integr Comp Physiol 2008 294 R528
Shankar, K Kang, P Harrell, A Maternal overweight programs insulin and adiponectin signaling in the offspring Endocrinology 2010 151 2577
Symonds, M E Heasman, L Clarke, L Maternal nutrition and disproportionate placental to fetal growth Biochem Soc Trans 1998 26 91
Wang, J Ma, H Tong, C Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart FASEB J 2010 24 2066
Samuelsson, A M Matthews, P A Argenton, M Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming Hypertension 2008 51 383
Massiera, F Barbry, P Guesnet, P A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations J Lipid Res 2010 51 2352
Lieb, W Pencina, M J Lanier, K J Association of parental obesity with concentrations of select systemic biomarkers in nonobese offspring: the Framingham Heart Study Diabetes 2009 58 134
Weisberg, S P McCann, D Desai, M Obesity is associated with macrophage accumulation in adipose tissue J Clin Invest 2003 112 1796
Wellen, K E Hotamisligil, G S Obesity-induced inflammatory changes in adipose tissue J Clin Invest 2003 112 1785
Yessoufou, A Moutairou, K Khan, N A A model of insulin resistance in mice, born to diabetic pregnancy, is associated with alterations of transcription-related genes in pancreas and epididymal adipose tissue J Obes 2011
Buckley, A J Keseru, B Briody, J Altered body composition and metabolism in the male offspring of high fat-fed rats Metabolism 2005 54 500
Korotkova, M Gabrielsson, B Hanson, L A Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups J Lipid Res 2001 42 359
Egger, G Dixon, J. Inflammatory effects of nutritional stimuli: further support for the need for a big picture approach to tackling obesity and chronic disease Obes Rev 2010 11 137
Kim, H K Della-Fera, M Lin, J Docosahexaenoic acid inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 preadipocytes J Nutr 2006 136 2965
Grant, W F Gillingham, M B Batra, A K Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates PLoS One 2011 6 e17261
Korotkova, M Gabrielsson, B Lonn, M Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet J Lipid Res 2002 43 1743
Massiera, F Saint-Marc, P Seydoux, J Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res 2003 44 271
Oken, E Kleinman, K P Olsen, S F Associations of seafood and elongated n-3 fatty acid intake with fetal growth and length of gestation: results from a US pregnancy cohort Am J Epidemiol 2004 160 774
Donahue, S M Rifas-Shiman, S L Gold, D R Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort Am J Clin Nutr 2011 93 780
Hauner, H Vollhardt, C Schneider, K T The impact of nutritional fatty acids during pregnancy and lactation on early human adipose tissue development. Rationale and design of the INFAT study Ann Nutr Metab 2009 54 97
Bispham, J Gardner, D S Gnanalingham, M G 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 2005 146 3943
Joss-Moore, L A Wang, Y Campbell, M S Uteroplacental insufficiency increases visceral adiposity and visceral adipose PPARgamma2 expression in male rat offspring prior to the onset of obesity Early Hum Dev 2010 86 179
Budge, H Sebert, S Sharkey, D Session on ‘Obesity’. Adipose tissue development, nutrition in early life and its impact on later obesity Proc Nutr Soc 2009 68 321
Pearce, S Casteilla, L Gualillo, O Differential effects of age and gender on the postnatal responsiveness of brown adipose tissue to prolactin administration in rats Exp Physiol 2003 88 527
Au-Yong, I T Thorn, N Ganatra, R Brown adipose tissue and seasonal variation in humans Diabetes 2009 58 2583
Symonds, M E Integration of physiological and molecular mechanisms of the developmental origins of adult disease: new concepts and insights Proc Nutr Soc 2007 66 442
Rousso-Noori, L Knobler, H Levy-Apter, E Protein tyrosine phosphatase epsilon affects body weight by downregulating leptin signaling in a phosphorylation-dependent manner Cell Metab 2011 13 562
Bayol, S A Simbi, B H Bertrand, J A Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females J Physiol 2008 586 3219
Korotkova, M Gabrielsson, B G Holmang, A Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids Am J Physiol Regul Integr Comp Physiol 2005 288 R575
Fowden, A L Harding, R Ralph, M M Nutritional control of respiratory and other muscular activities in relation to plasma prostaglandin E in the fetal sheep J Dev Physiol 1989 11 253