title: A common cause for a common phenotype: the gatekeeper hypothesis in fetal programming.
abstract: Sub-optimal nutrition during pregnancy has been shown to have long-term effects on the health of offspring in both humans and animals. The most common outcomes of such programming are hypertension, obesity, dyslipidaemia and insulin resistance. This spectrum of disorders, collectively known as metabolic syndrome, appears to be the consequence of nutritional insult during early development, irrespective of the nutritional stress experienced. For example, diets low in protein diet, high in fat, or deficient in iron are all associated with programming of cardiovascular and metabolic disorders when fed during rat pregnancy. In this paper, we hypothesise that the nutritional stresses act on genes or gene pathways common to all of the insults. We have termed these genes and/or gene pathways the "gatekeepers" and hence developed the "gatekeeper hypothesis". In this paper, we examine the background to the hypothesis and postulate some possible mechanisms or pathways that may constitute programming gatekeepers.
authors: School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK.
authors: S
authors: S
authors: McMullen
authors: S C
authors: SC
authors: Langley-Evans
authors: L
authors: L
authors: Gambling
authors: C
authors: C
authors: Lang
authors: A
authors: A
authors: Swali
authors: H J
authors: HJ
authors: McArdle
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D048070:Fetal Nutrition Disorders / Q000503:physiopathology*; D006801:Humans; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000209:etiology*; D008954:Models, Biological; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D015398:Signal Transduction / Q000235:genetics*; D014481:United States / Q000453:epidemiology