The impact of maternal body composition and dietary fat consumption upon placental lipid processing and offspring metabolic health

The proportion of women of reproductive age who are overweight or obese is increasing globally. Gestational obesity is strongly associated in both human studies and animal models with early-onset development of adult-associated metabolic diseases including metabolic syndrome in the exposed offspring. However, animal model studies have suggested that gestational diet in obese pregnancies is an independent but underappreciated mediator of offspring risk for later life metabolic disease, and human diet consumption data have highlighted that many women do not follow nutritional guidelines prior to and during pregnancy. Thus, this review will highlight how maternal diet independent from maternal body composition impacts the risk for later-life metabolic disease in obesity-exposed offspring. A poor maternal diet, in combination with the obese metabolic state, are understood to facilitate pathological in utero programming, specifically through changes in lipid handling processes in the villous trophoblast layer of the placenta that promote an environment associated with the development of metabolic disease in the offspring. This review will additionally highlight how maternal obesity modulates villous trophoblast lipid processing functions including fatty acid transport, esterification and beta-oxidation. Further, this review will discuss how altering maternal gestational diet may ameliorate these functional changes in lipid metabolic processes in the obese placenta

Nutrition in Pregnancy: Volume I

Maternal nutrition during pregnancy is of considerable interest to women, their partners and their health care professionals. In developing countries, maternal undernutrition is a major concern. However, with the increased prevalence of abundant high calorie diets, their impact upon pregnancy outcome is of concern. In addition to the amount of nutrition available and its macronutrient composition within a diet, there is emerging evidence highlighting important roles for the lesser studied micronutrients. Added to this complexity is the distinction between maternal and fetal nutrition and the impact the placenta plays in nutrient metabolism and overall nutrient supply to the fetus. Together, these many variables contribute to placental development and function, fetal growth, and, where placental/fetal nutrition and growth is compromised, through poor maternal diet, and/or diet induced alterations in placental metabolism, the impact is dramatic and can lead to lifelong implications for the offspring. This Special Issue book aims to highlight research in many of these areas

In utero programming of later adiposity: The role of fetal growth restriction

Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all contribute to an increased later life obesity risk. Data suggest that many of these changes result from an enhanced activity of the adipose master transcription factor regulator, peroxisome proliferator-activated receptor-γ (PPARγ) and its coregulators, increased lipogenic fatty acid synthase (FAS) expression and activity, and upregulation of glycolysis in fetal adipose tissue. Increased expression of fetal hypothalamic neuropeptide Y (NPY), altered hypothalamic leptin receptor expression and partitioning, reduced adipose noradrenergic sympathetic innervations, enhanced adipose glucocorticoid action, and modifications in methylation status in the promoter of hepatic and adipose adipogenic and lipogenic genes in the fetus also contribute to obesity following IUGR. Therefore, interventions that inhibit these fetal developmental changes will be beneficial for modulation of adult body fat accumulation. © 2012 Ousseynou Sarr et al

The long and short of it: The role of telomeres in fetal origins of adult disease

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes. © 2012 Stephanie E. Hallows et al

Extraordinarily rapid proliferation of cultured muscle satellite cells from migratory birds

Migratory birds experience bouts of muscle growth and depletion as they prepare for, and undertake prolonged flight. Our studies of migratory bird muscle physiology in vitro led to the discovery that sanderling (Calidris alba) muscle satellite cells proliferate more rapidly than other normal cell lines. Here we determined the proliferation rate of muscle satellite cells isolated from five migratory species (sanderling; ruff, Calidris pugnax; western sandpiper, Calidris mauri; yellow-rumped warbler, Setophaga coronata; Swainson\u27s thrush, Catharus ustulatus) from two families (shorebirds and songbirds) and with different migratory strategies. Ruff and sanderling satellite cells exhibited rapid proliferation, with population doubling times of 9.3 ± 1.3 and 11.4 ± 2 h, whereas the remaining species\u27 cell doubling times were greater than or equal to 24 h. The results indicate that the rapid proliferation of satellite cells is not associated with total migration distance but may be related to flight bout duration and interact with lifespan

Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity

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

Chronic intrauterine hypoxia interferes with aortic development in the late gestation ovine fetus

This study explored arterial remodelling in fetuses growth restricted by hypoxia. Chronically catheterized fetal sheep were made moderately or severely hypoxic by placental embolization for 15 days starting at gestational age 116-118 (term ∼147 days). Cross-sections of the aorta were analysed for collagen and elastin content using histological procedures, while immunofluorescence was applied to measure markers of vascular smooth muscle cell (VSMC) type. In frozen aortae quantitative PCR was used to measure mRNA levels of extracellular matrix (ECM) precursor proteins as well as molecular regulators of developmental and pathological remodelling. Relative to Control (n= 6), aortic wall thickness was increased by 23% in the Moderate group (n= 5) and 33% (P \u3c 0.01) in the Severe group (n= 5). Relative to Control, the Severe group exhibited a 5-fold increase in total collagen content (P \u3c 0.01) that paralleled increases in mRNA levels of procollagen I (P \u3c 0.05) and III and transforming growth factor β (TGF-β 1) (P \u3c 0.05). The percentage area stained for α-actin was inversely related to fetal arterial oxygen saturation (P \u3c 0.05) and total α-actin content was 45% higher in the Moderate group and 65% (P \u3c 0.05) higher in the Severe group, compared to Control. A 12% and 39% (P \u3c 0.05) reduction in relative elastic fibre content was observed in Moderate and Severe fetuses, respectively. mRNA levels of the elastolytic enzyme, matrix metalloproteinase-2 (MMP-2) were inversely correlated with fetal arterial oxygen saturation (P \u3c 0.05) (Fig. 7) and mRNA levels of its activator, membrane-type MMP (MTI-MMP), were elevated in the Severe group (P \u3c 0.05). Marked neointima formation was apparent in Severe fetuses (P \u3c 0.05) concomitant with an increase in E-selectin mRNA expression (P \u3c 0.05). Thus, aberrant aortic formation in utero mediated by molecular regulators of arterial growth occurs in response to chronic hypoxaemia. © 2011 The Authors. Journal compilation © 2011 The Physiological Society

Low birth weight followed by postnatal over-nutrition in the guinea pig exposes a predominant player in the development of vascular dysfunction

The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length-tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and aorta using wire myography. Relative to NBW/CD, aortae of NBW/WD offspring were stiffer, as determined by a leftward shift in the length-tension curve, yet the shift in the LBW/CD curve was considerably greater. Aortic stiffening was most severe in LBW/WD (slope: NBW/CD, 1.97 ± 0.04; NBW/WD, 2.16 ± 0.04; LBW/CD, 2.28 ± 0.05; LBW/WD, 2.34 ± 0.07). Maximal responses (Emax) to MCh were significantly blunted in the aorta of LBW/CD vs. NBW/CD (P \u3c 0.05) and in LBW/WD vs. NBW/WD offspring (P \u3c 0.05); but WD alone had no influence on MCh responses. Emax values for carotid responses to MCh were reduced in LBW/CD vs. NBW/CD (P \u3c 0.05). Thus, aortic stiffening was influenced more by LBW than by a postnatal WD and the most severe stiffening was observed in LBW/WD offspring. In contrast, blunted endothelial responses in LBW/CD offspring were not exacerbated by WD. IUGR may have a greater independent impact on vascular function than a postnatal WD