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.

Postnatal catch-up fat after late preterm birth

“…There is evidence that monitoring not only the quantity but also the quality of growth, in terms of body composition changes, may play an important role in gaining further insight into the relationship between birth weight and time in utero on early growth pattern and future health (4)(5)(6). Indeed, extremely preterm infants, assessed at term-corrected age, have been found to be at increased risk for developing increased and/or aberrant adiposity, which is a known risk marker for cardiovascular disease (7,8).…”

Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth

“…Insulin resistance is considered to be a fundamental contributor to metabolic syndrome (1)(2)(3). The underlying causes of IUGR are complicated.…”

Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease

“…Studies in adults and children born SGA indicate that insulin resistance is the earliest component associated with low birthweight, irrespective of confounding factors, including obesity and a family history of T2DM [37][38][39]. Nutrition in an adverse intrauterine environment during foetal life can be able to trigger a metabolic adaptation by epigenetic regulation of gene expression and thereby permanently sets functional capacity, metabolic competence, and responses to the later environment that favour NAFLD [40]. Furthermore, liver growth itself may be impaired and reduced as part of the adaptive response to a poor foetal substrate supply [40].…”

“…Nutrition in an adverse intrauterine environment during foetal life can be able to trigger a metabolic adaptation by epigenetic regulation of gene expression and thereby permanently sets functional capacity, metabolic competence, and responses to the later environment that favour NAFLD [40]. Furthermore, liver growth itself may be impaired and reduced as part of the adaptive response to a poor foetal substrate supply [40].…”