Nutrition–hormone receptor–gene interactions: implications for development and disease

Abstract

Nutrition profoundly alters the phenotypic expression of a given genotype, particularly during fetal and postnatal development. Many hormones act as nutritional signals and their receptors play a key role in mediating the effects of nutrition on numerous genes involved in differentiation, growth and metabolism. Polypeptide hormones act on membrane-bound receptors to trigger gene transcription via complex intracellular signalling pathways. By contrast, nuclear receptors for lipid-soluble molecules such as glucocorticoids (GC) and thyroid hormones (TH) directly regulate transcription via DNA binding and chromatin remodelling. Nuclear hormone receptors are members of a large superfamily of transcriptional regulators with the ability to activate or repress many genes involved in development and disease. Nutrition influences not only hormone synthesis and metabolism but also hormone receptors, and regulation is mediated either by specific nutrients or by energy status. Recent studies on the role of early environment on development have implicated GC and their receptors in the programming of adult disease. Intrauterine growth restriction and postnatal undernutrition also induce striking differences in TH-receptor isoforms in functionally-distinct muscles, with critical implications for gene transcription of myosin isoforms, glucose transporters, uncoupling proteins and cation pumps. Such findings highlight a mechanism by which nutritional status can influence normal development, and modify nutrient utilization, thermogenesis, peripheral sensitivity to insulin and optimal cardiac function. Diet and stage of development will also influence the transcriptional activity of drugs acting as ligands for nuclear receptors. Potential interactions between nuclear receptors, including those for retinoic acid and vitamin D, should not be overlooked in intervention programmes using I or vitamin A supplementation of young and adult human populations.

New insights into nutrition and cognitive neuroscience

“…Considerable progress has now been made in understanding the molecular mechanisms and neural pathways underlying the effects of nutrition on mental health. Cellular and nuclear receptors play a key role in mediating nutritional effects on function (56,(68)(69)(70) . They enable sophisticated regulation of numerous genes involved in neural function and brain plasticity.…”

Recent advances in nutrition, genes and brain health

“…Many other signalling molecules are involved (50)(51)(52) . For example, insulin-like growth factor-1 mediates the actions of BDNF, and the histone deacetylase sirtuin silent information regulator 1 is modified by energy metabolism.…”

“…Glucocorticoids, thyroid hormones and other ligands of the nuclear receptor super-family may also play a pivotal role. Their receptors act as transcription factors to affect multiple genes via epigenetic changes involving histone acetylation and chromatin remodelling (50,58) .…”

“…Energy status throughout the life-cycle influences numerous hormones and growth factors (50,51) . These act as nutritional sensors to influence brain structure and function via changes in gene expression.…”

Nutrition in the expression of reproductive potential

“…In the case of the reproducing animal this link has additional importance in that nutrients are not just involved in cell proliferation and tissue growth but also in the exquisitely sensitive processes of cell and tissue differentiation that ensure normality of form and function in the neonate. The actions of nutrients are both direct, as in the provision of essential substrates, and indirect through their ability to alter the expression of the numerous maternal and foetal endocrine mechanisms that operate during reproduction (Dauncey et al, 2001). These influence the availability and utilization of nutrients at the cell and tissue level.…”