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Am J Physiol Endocrinol Metab 279: E83-E87, 2000;
0193-1849/00 $5.00
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Vol. 279, Issue 1, E83-E87, July 2000

Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition

Mark H. Vickers, Bernhard H. Breier, Wayne S. Cutfield, Paul L. Hofman, and Peter D. Gluckman

Research Centre for Developmental Medicine and Biology, Faculty of Medicine and Health Science, University of Auckland, 92019 Auckland, New Zealand

Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause. Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming. Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease. Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (AD group) or at 30% of ad libitum intake, or undernutrition (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring. At weaning, offspring were assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet]. Food intake in offspring from UN mothers was significantly elevated at an early postnatal age. It increased further with advancing age and was amplified by hypercaloric nutrition. UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations. This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development.

appetite; insulin resistance; leptin resistance; cardiovascular disease


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J. Physiol., December 1, 2004; 561(2): 355 - 377.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
B. de Vrijer, T. R. H. Regnault, R. B. Wilkening, G. Meschia, and F. C. Battaglia
Placental uptake and transport of ACP, a neutral nonmetabolizable amino acid, in an ovine model of fetal growth restriction
Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1114 - E1124.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
A. Varma, J. He, B.-C. Shin, L. A. Weissfeld, and S. U. Devaskar
Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype
Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1132 - E1141.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
S. R. Ravelich, A. N. Shelling, A. Ramachandran, S. Reddy, J. A. Keelan, D. N. Wells, A. J. Peterson, R. S.F. Lee, and B. H. Breier
Altered Placental Lactogen and Leptin Expression in Placentomes from Bovine Nuclear Transfer Pregnancies
Biol Reprod, December 1, 2004; 71(6): 1862 - 1869.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
P. L. Hofman, F. Regan, W. E. Jackson, C. Jefferies, D. B. Knight, E. M. Robinson, and W. S. Cutfield
Premature Birth and Later Insulin Resistance
N. Engl. J. Med., November 18, 2004; 351(21): 2179 - 2186.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
M. A. Sperling
Prematurity -- A Window of Opportunity?
N. Engl. J. Med., November 18, 2004; 351(21): 2229 - 2231.
[Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
S. P. Bagby
Obesity-Initiated Metabolic Syndrome and the Kidney: A Recipe for Chronic Kidney Disease?
J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2775 - 2791.
[Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
G. S. Gopalakrishnan, D. S. Gardner, S. M. Rhind, M. T. Rae, C. E. Kyle, A. N. Brooks, R. M. Walker, M. M. Ramsay, D. H. Keisler, T. Stephenson, et al.
Programming of adult cardiovascular function after early maternal undernutrition in sheep
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R12 - R20.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
K. R. Poore and A. L. Fowden
The effects of birth weight and postnatal growth patterns on fat depth and plasma leptin concentrations in juvenile and adult pigs
J. Physiol., July 1, 2004; 558(1): 295 - 304.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. He, A. Varma, L. A. Weissfeld, and S. U. Devaskar
Postnatal glucocorticoid exposure alters the adult phenotype
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R198 - R208.
[Abstract] [Full Text] [PDF]

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 Reproductive SciencesHome page
M. A. El-Haddad, M. Desai, D. Gayle, and M. G. Ross
In Utero Development of Fetal Thirst and Appetite: Potential for Programming
Reproductive Sciences, April 1, 2004; 11(3): 123 - 130.
[Abstract] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. Chen, T. Zhang, and B. L. G. Nyomba
Insulin resistance of gluconeogenic pathways in neonatal rats after prenatal ethanol exposure
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2004; 286(3): R554 - R559.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
L. Chen and B. L. G. Nyomba
Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure
J Appl Physiol, January 1, 2004; 96(1): 167 - 172.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. Bennet and A. J. Gunn
Memories of the fetal heart
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R517 - R518.
[Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. H. Vickers, B. H. Breier, D. McCarthy, and P. D. Gluckman
Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R271 - R273.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Varma, J. He, L. Weissfeld, and S. U. Devaskar
Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1560 - R1566.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. L. Kind, P. M. Clifton, P. A. Grant, P. C. Owens, A. Sohlstrom, C. T. Roberts, J. S. Robinson, and J. A. Owens
Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R140 - R152.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
K G Tantisira and S T Weiss
Complex interactions in complex traits: obesity and asthma
Thorax, September 1, 2001; 56(90002): ii64 - 74.
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