Abstract
The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.
Highlights
Recent clinical, epidemiological and animal studies have highlighted an association between an altered, adverse in utero environment and growth, and the subsequent propensity of these offspring to develop hallmarks of the metabolic syndrome [1,2,3]
protein kinase C (PKC)-θ activation itself has been reported to occur during a state of lipid overload in skeletal muscle, and may represent an alternative pathway mediating alterations in the serine/threonine phosphorylation status of key insulin signaling intermediates [25,61]. Direct evidence that these changes may be happening in low birth weight intrauterine growth restriction (IUGR) offspring as they age is still lacking, but if occurring, presents a potential pathway where in utero induced changes in fatty acid oxidation may play a contributing role to later life insulin resistance when challenged with a postnatal high fat diet
Infants of an adverse in utero environment represent a unique population who appear to be at a greater risk for the development of insulin resistance and subsequent metabolic disease [1,5,18]
Summary
Epidemiological and animal studies have highlighted an association between an altered, adverse in utero environment and growth, and the subsequent propensity of these offspring to develop hallmarks of the metabolic syndrome [1,2,3]. Rodent models of low birth weight have demonstrated a decrease in skeletal muscle mass [19], similar to the altered muscle to fat ratio observed in older men who were born low birth weight [20] With this altered development there are metabolic changes to the offspring, resulting in what has been proposed as a “thrifty phenotype” [1,18]. Represents the observable phenotype associated with IUGR, theories of fetal programming postulate that altered oxygen and nutrient transfer during critical windows of development, when the fetus is most sensitive to its environment, are associated with permanent alterations in structure and metabolism, and a fixed functional capacity of vital organs in postnatal life [1]. The mechanisms underlying these alterations in the metabolic capacity of the IUGR fetus and their propensity towards the development of later life insulin resistance and the metabolic syndrome remain poorly defined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
