title: Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity.
abstract: There is an association between growing slowly before birth, accelerated growth in early postnatal life and the emergence of insulin resistance, visceral obesity and glucose intolerance in adult life. In this review we consider the pathway through which intrauterine growth restriction (IUGR) leads to the initial increase in insulin sensitivity and to catch-up growth. We also discuss the importance of the early insulin environment in determining later visceral adiposity and the intrahepatic mechanisms that may result in the emergence of glucose intolerance in a subset of IUGR infants. We present evidence that a key fetal adaptation to poor fetal nutrition is an upregulation of the abundance of the insulin receptor in the absence of an upregulation of insulin signalling in fetal skeletal muscle. After birth, however, there is an upregulation in the abundance of the insulin receptor and the insulin signalling pathway in the IUGR offspring. Thus, the origins of the accelerated postnatal growth rate experienced by IUGR infants lie in the fetal adaptations to a poor nutrient supply. We also discuss how the intracellular availability of free fatty acids and glucose within the visceral adipocyte and hepatocyte in fetal and neonatal life are critical in determining the subsequent metabolic phenotype of the IUGR offspring. It is clear that a better understanding of the relative contributions of the fetal and neonatal nutrient environment to the regulation of key insulin signalling pathways in muscle, visceral adipose tissue and the liver is required to support the development of evidence-based intervention strategies and better outcomes for the IUGR infant.
authors.affiliation: Sansom Institute of Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Duffield
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Muhlhausler
authors.forename: Sheridan
authors.initials: S
authors.lastname: Gentili
authors.forename: Isabella C
authors.initials: IC
authors.lastname: McMillen
mesh_terms: D050153:Abdominal Fat / Q000503:physiopathology*; D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D024821:Metabolic Syndrome / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D007328:Insulin