Metabolic plasticity during mammalian development is directionally dependent on early nutritional status - PubMed (original) (raw)

Metabolic plasticity during mammalian development is directionally dependent on early nutritional status

Peter D Gluckman et al. Proc Natl Acad Sci U S A. 2007.

Abstract

Developmental plasticity in response to environmental cues can take the form of polyphenism, as for the discrete morphs of some insects, or of an apparently continuous spectrum of phenotype, as for most mammalian traits. The metabolic phenotype of adult rats, including the propensity to obesity, hyperinsulinemia, and hyperphagia, shows plasticity in response to prenatal nutrition and to neonatal administration of the adipokine leptin. Here, we report that the effects of neonatal leptin on hepatic gene expression and epigenetic status in adulthood are directionally dependent on the animal's nutritional status in utero. These results demonstrate that, during mammalian development, the direction of the response to one cue can be determined by previous exposure to another, suggesting the potential for a discontinuous distribution of environmentally induced phenotypes, analogous to the phenomenon of polyphenism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Fig. 1.

Fetal nutrition induces a bifurcation in the response of 11β-HSD2 gene expression to leptin treatment. We measured mRNA expression of the 11β-HSD2 gene in the livers of adult (170-day-old) female rats exposed in utero to maternal undernutrition (UN) or ad libitum feeding (AD), treated with saline or leptin from days 3–10 of life, and then fed normal chow (Upper) or a high-fat diet (Lower) from weaning. Maternal nutrition altered the direction of the response of 11β-HSD2 expression to neonatal leptin treatment (test for reversal of sign of response, P < 0.01; test for interaction between prenatal nutrition and leptin administration, P < 0.0001); the effect was independent of postweaning nutrition. Data are means ± SEM for n = 8 per group; values are expressed relative to that of normally nourished (maternally ad libitum-fed and postweaning chow-fed) and saline-treated offspring set as 100%.

Fig. 2.

Fig. 2.

Neonatal leptin treatment normalizes gross phenotype (adiposity) and hepatic gene expression in adult rats exposed to undernutrition in utero followed by hypercaloric nutrition after weaning. We measured total body fat (dual-energy x-ray absorptiometry) (Left) and hepatic mRNA expression (Right) of adult (170-day-old) female rats that had been subject in utero to maternal undernutrition (UN) or ad libitum feeding (AD), treated with saline or leptin from days 3–10 of life, and then fed normal chow or a high-fat diet from weaning. Data are means ± SEM for n = 8 per group; values for gene expression are expressed relative to those of normally nourished (maternally ad libitum-fed and postweaning chow-fed) and saline-treated offspring set as 100%. Data for total body fat are replotted from Vickers et al. (13). *, P < 0.05: significantly different from normally nourished, saline-treated animals. †, P < 0.05: significant effect of leptin treatment in UN high-fat animals.

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References

    1. Gluckman PD, Hanson MA, Spencer HG, Bateson P. Proc Biol Sci. 2005;272:671–677. - PMC - PubMed
    1. West-Eberhard MJ. Developmental Plasticity and Evolution. New York: Oxford Univ Press; 2003.
    1. Applebaum SW, Heifetz Y. Annu Rev Entomol. 1999;44:317–341. - PubMed
    1. Evans JD, Wheeler DE. Proc Natl Acad Sci USA. 1999;96:5575–5580. - PMC - PubMed
    1. Gluckman PD, Hanson MA, Beedle AS. Am J Hum Biol. 2007;19:1–19. - PubMed

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