Effect of intrauterine growth retardation on liver and long-term metabolic risk

Abstract

Intrauterine growth retardation predisposes toward long-term morbidity from type 2 diabetes and cardiovascular disease. To explain this association, the concept of programming was introduced to indicate a process whereby a stimulus or insult at a critical period of development has lasting or lifelong consequences on key endocrine and metabolic pathways. Subtle changes in cell composition of tissues, induced by suboptimal conditions in utero, can influence postnatal physiological functions. There is increasing evidence, suggesting that liver may represent one of the candidate organs targeted by programming, undergoing structural, functional and epigenetic changes following exposure to an unfavorable intrauterine environment. The aim of this review is to provide insights into the molecular mechanisms underlying liver programming that contribute to increase the cardiometabolic risk in subjects with intrauterine growth restriction.

Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep

“…Previous studies have pointed to the liver as a key target of maternal malnutrition during critical periods of foetal development (Cianfarani et al . ), and in a previous sheep study, we have found that prenatal undernutrition is associated with alterations in the fatty acid composition of hepatic phospholipids and upregulation of key target genes involved in hepatic insulin signalling and carbohydrate and lipid metabolism, such as INSR β (insulin receptor beta subunit) and PI3K‐p110 (phosphatidylinositol 3‐kinases p110 beta catalytic subunit; Hou et al . ).…”

“…Previous studies have pointed to the liver as a key target of maternal malnutrition during critical periods of foetal development (Cianfarani et al 2012), and in a previous sheep study, we have found that prenatal undernutrition is associated with alterations in the fatty acid composition of hepatic phospholipids and upregulation of key target genes involved in hepatic insulin signalling and carbohydrate and lipid metabolism, such as INSRb (insulin receptor beta subunit) and PI3K-p110 (phosphatidylinositol 3-kinases p110 beta catalytic subunit; Hou et al 2013). Assuming that the liver was the major organ accounting for acute changes in lactate profiles observed during the different tolerance tests, it is therefore tempting to speculate that the prenatal impacts on lactate profiles may also be related to altered hepatic metabolic function.…”

Differential developmental programming by early protein restriction of rat skeletal muscle according to its fibre‐type composition

“…It is now well established that an unbalanced nutritional environment in utero or during neonatal life induces a high risk of developing obesity and related metabolic disorders in adulthood (Fernandez-Twinn & Ozanne 2010, Wiedmeier et al 2011. This enhanced disease susceptibility, named developmental or metabolic programming, has been associated with impaired structure and function of several organs including brain (Grace et al 2011), liver (Cianfarani et al 2012), pancreas (Reusens et al 2011) and skeletal muscle. In regard to this latter tissue, it has been shown that reduced nutrient supply during the last 3 days of gestation, induced by the ligation of the uterine artery, leads to decreased ATP production and reduced glucose transport and glycogen biosynthesis in red muscle (Selak et al 2003).…”

A Molecular Perspective on Procedures and Outcomes with Assisted Reproductive Technologies

“…Exposures during pregnancy leading to IUGR have been linked to long-term undesirable outcomes in the offspring such as obesity, metabolic syndrome, and a predisposition toward long-term morbidity from type 2 diabetes and cardiovascular disease. Growing evidence suggests that the liver may represent one of the candidate organs targeted by programming, undergoing structural, functional, and epigenetic changes following exposure to an unfavorable intrauterine environment (Cianfarani et al 2012). Low-birth weight and babies delivered preterm may represent populations at risk of long-term metabolic disorders and may be valuable cohorts to study the role of epigenetic programming.…”