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

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.developmental plasticity ͉ epigenetics ͉ gene expression ͉ leptin ͉ obesity

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

“…It may act directly or indirectly on those epigenetic processes regulating metabolic canalization. 20 It may be acting by effects on neonatal food intake, but this seems unlikely given that large changes in infant food intake in this model cause only minor modification of the adult phenotype. There is evidence that leptin has effects on the maturation of hypothalamic circuits controlling food intake, 57 and a key question is whether there is a critical period that is accessible in other species, such as the human, that are more mature at birth.…”

“…19,20 These are not parentally imprinted genes, supporting a role for nonimprinted epigenetic change in the regulation of developmental plasticity.…”

“…18 But developmental plasticity operates within the normative range of developmental environments, and there is growing evidence that there is extensive and specific regulation of non-imprinted genes in such environmentally regulated plasticity. [19][20][21][22] As developmental plasticity is basically an adaptive process, it seems more likely that it will be non-parentally imprinted genes that will be primarily involved in developmental pathways to obesity.…”

“…54,55 This in turn is associated with reversal of the changes in metabolic gene expression and methylation of these genes in liver tissue when examined as adults. 20 There are gender differences, 55,56 either reflecting the different role of body mass in reproductive success across the genders or different timings of maturation between species. The mode of action of leptin is speculative.…”

Early nutrition and phenotypic development: ‘catch-up’ growth leads to elevated metabolic rate in adulthood

“…The most probable cause of such an effect is the pattern of nutrition during growth and development. It has been suggested that physiological traits are set, often referred to as being 'programmed', by the nutritional environment experienced during early growth (Desai et al 1995;Gluckman et al 2007) as a result of tissue remodelling or changes in cell differentiation, organ growth and/or cell signalling (Bertram et al 2001;McMillen & Robinson 2005;Langley-Evans 2006).…”