Maternal High-Fat Diet Programs for Metabolic Disturbances in Offspring despite Leptin Sensitivity

Volpato, Ana Maria; Schultz, Alini; Magalhães-da-Costa, Eduardo; Correia, Marcelo; Águila, Márcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1159/000336377

Cited by 53 publications

(43 citation statements)

References 91 publications

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“…These results indicated that maternal HLE diet during gestation itself might program the development without obesity. Other researchers also observed the absence of obesity during gestation in rodents fed with HLE diet ( 30 ). Because chronic high-fat diet consumption may result in a greater lipid transfer to the fetus regardless of maternal obesity ( 9 ), the total lipid content in neonate and weaning mouse livers was signifi cantly increased in the HLE diet group in our study.…”

Section: Discussionsupporting

confidence: 73%

Adaptive responses by mouse fetus to a maternal HLE diet by downregulating SREBP1: a microarray- and bio-analytic-based study

Miao

Gao

et al. 2013

Journal of Lipid Research

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health problems as the ones observed in epidemiological studies ( 4,5 ). So, maternal high-fat diet is an important predisposing factor to the onset and development of obesity, insulin resistance, and cardiovascular diseases in offspring ( 6 ). Indeed, a high-fat diet during gestation has been shown to lead to a lack of increase in insulin release and ATP content in response to glucose stimulation in islets from 3-month-old male and female offspring ( 5 ).However, the mechanisms linking high-fat nutrition in early life with later health problems remain unclear. Preliminary work has been performed on several candidate mechanisms, including: 1 ) white adipose tissue glucocorticoid sensitivity ( 7 ); 2 ) gene modifi cation status, such as DNA methylation (epigenetic mechanism) ( 4 ); 3 ) oxidative stress in dams, which might be transferred to the pups during gestation, later promoting disease development in the offspring ( 8 ); and 4 ) a maternal high-fat diet by itself, which triggers lipotoxicity in the fetal livers and later affects the offspring's health status ( 9 ). Indeed, the metabolic alterations usually observed during pregnancy combined with increased dietary fat intake, increase the triglycerides available to be hydrolyzed for transfer to the offspring, inducing an adaptive toxic response in the offspring's liver; this lipotoxicity leads to macrophage infi ltration into the liver, and to increased cytokine secretion. This infl ammatory state activates the pathways involved in oxidative stress and in gluconeogenesis ( 9 ). These conditions may predispose the offspring to alterations in their lipid metabolism in adult life.An understanding of how maternal nutrients infl uence offspring's development of adult diseases may be gained using proteomic methodologies and microarray analyses.Abstract Maternal diet has long been recognized as a signifi cant factor affecting offspring development and health, but the target genes affected by a maternal high-lipid diet are currently unknown. In this study, the gene expression profi le of neonatal mouse liver was analyzed using gene chips to identify genes with signifi cant up-or downregulated expression levels due to maternal high-fat diet during gestation. Real-time PCR and Western blotting were used to measure key genes selected using microarray. Serum lipid, glucose, and insulin levels in adult offspring from dams fed with chow or a high-lipid diet were measured using commercial kits. Results indicate that the expression of genes involved in cholesterol and fatty acid synthesis were signifi cantly inhibited, while the expression of genes involved in glycolysis were signifi cantly decreased by maternal high-lipid diet during gestation. SREBP1 might be the key gene regulating genes involved in fatty acid, glucose, and cholesterol metabolism in response to a maternal high-fat diet. Maternal nutrient intake during gestation has long been recognized as a signifi cant factor affecting the incidence of features of the adult metabolic syndrome in offspring. Indeed, human ...

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Section: Discussionsupporting

confidence: 73%

Adaptive responses by mouse fetus to a maternal HLE diet by downregulating SREBP1: a microarray- and bio-analytic-based study

Miao

Gao

et al. 2013

Journal of Lipid Research

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“…Offspring exposed to a maternal HFD in utero and/or postnatally developed manifestations of the Metabolic Syndrome, such as insulin resistance, increased liver mass and triglyceride content, hepatic steatosis, increased visceral fat mass and adipocyte hypertrophy but not central leptin resistance [30, 41]. These changes are accompanied by increased serum concentrations of tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) [30].…”

Section: Mousementioning

confidence: 99%

“…Similar changes are observed even when the offspring are weaned to a non-HFD. Interestingly, exposure to HFD in utero has a more detrimental effect on the liver of the offspring than does HFD after weaning [41]. Moderate steatosis and NASH has been shown to be associated with increased expression of genes of lipogenesis, oxidative stress and inflammation, in addition to alterations in activity of enzymes of the electron transport chain [37, 47].…”

Section: Mousementioning

confidence: 99%

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Animal models of in utero exposure to a high fat diet: A review

Williams

Seki

Vuguin

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

187

161

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The incidence of metabolic disease, including type 2 diabetes and obesity, has increased to epidemic levels in recent years. A growing body of evidence suggests that the intrauterine environment plays a key role in the development of metabolic disease in offspring. Among other perturbations in early life, alteration in the provision of nutrients has profound and lasting effects on the long term health and well being of offspring. Rodent and non-human primate models provide a means to understand the underlying mechanisms of this programming effect. These different models demonstrate converging effects of a maternal high fat diet on insulin and glucose metabolism, energy balance, cardiovascular function and adiposity in offspring. Furthermore, evidence suggests that the early life environment can result in epigenetic changes that set the stage for alterations in key pathways of metabolism that lead to type 2 diabetes or obesity. Identifying and understanding the causal factors responsible for this metabolic dysregulation is vital to curtailing these epidemics.

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“…Compared to a healthy offspring diet, a post-weaning Western-type offspring diet exacerbated the effects of the mother’s obesity on weight gain or adiposity (Bayol et al, 2007; Chen et al, 2009; Ong and Muhlhausler, 2014; White et al, 2009), glucose/insulin regulation (Arentson-Lantz et al, 2014; Benkalfat et al, 2011; Chen et al, 2009; Flynn et al, 2013; Khanal et al, 2014; Li et al, 2013; Page et al, 2009; Rajia et al, 2010; Shalev et al, 2010; Srinivasan et al, 2006; Volpato et al, 2012), cardiovascular measures (Elahi et al, 2009; Fan et al, 2013; Turdi et al, 2013), or fatty liver (Bouanane et al, 2010; Bruce et al, 2009; Hellgren et al, 2014; Li et al, 2013; Mouralidarane et al, 2013; Pruis et al, 2014; Zhang et al, 2013) in the offspring in most studies. For example, Chen and colleagues report that homeostatic model assessment of insulin resistance (HOMA-IR) was similar among rat offspring with high fat prenatal diet alone (0.46) compared to control prenatal and post-weaning diet (0.35); elevated among those with control prenatal and high fat post-weaning diet (0.62); and dramatically elevated among those with high fat control and post-weaning diet combined (1.15; p for interaction>0.05) (Chen et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

From fatalism to mitigation: A conceptual framework for mitigating fetal programming of chronic disease by maternal obesity

Boone‐Heinonen

Messer

Fortmann

et al. 2015

Preventive Medicine

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Prenatal development is recognized as a critical period in the etiology of obesity and cardiometabolic disease. Potential strategies to reduce maternal obesity-induced risk later in life have been largely overlooked. In this paper, we first propose a conceptual framework for the role of public health and preventive medicine in mitigating the effects of fetal programming. Second, we review a small but growing body of research (through August 2015) that examines interactive effects of maternal obesity and two public health foci – diet and physical activity – in the offspring. Results of the review support the hypothesis that diet and physical activity after early life can attenuate disease susceptibility induced by maternal obesity, but human evidence is scant. Based on the review, we identify major gaps relevant for prevention research, such as characterizing the type and dose response of dietary and physical activity exposures that modify the adverse effects of maternal obesity in the offspring. Third, we discuss potential implications of interactions between maternal obesity and postnatal dietary and physical activity exposures for interventions to mitigate maternal obesity-induced risk among children. Our conceptual framework, evidence review, and future research directions offer a platform to develop, test, and implement fetal programming mitigation strategies for the current and future generations of children.

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Maternal High-Fat Diet Programs for Metabolic Disturbances in Offspring despite Leptin Sensitivity

Cited by 53 publications

References 91 publications

Adaptive responses by mouse fetus to a maternal HLE diet by downregulating SREBP1: a microarray- and bio-analytic-based study

Adaptive responses by mouse fetus to a maternal HLE diet by downregulating SREBP1: a microarray- and bio-analytic-based study

Animal models of in utero exposure to a high fat diet: A review

From fatalism to mitigation: A conceptual framework for mitigating fetal programming of chronic disease by maternal obesity

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