Increased Hepatic Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Rat Model of Intrauterine Growth Retardation and Subsequent Insulin Resistance

Lane, Robert H.; MacLennan, Nicole K.; Hsu, Jennifer L.; Janke, Sara M.; Pham, Tho D.

doi:10.1210/endo.143.7.8898

Cited by 66 publications

(16 citation statements)

References 27 publications

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“…In the rat, IUGR induced by bilateral uterine artery ligation in late pregnancy results in fasting hyperglycemia and hyperinsulinemia in later life [51,52]. In this model peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α) is increased in the livers of the offspring at birth and at 21 days of life [52].…”

Section: Iugr Liver Growth and Metabolic Developmentmentioning

confidence: 99%

“…In this model peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α) is increased in the livers of the offspring at birth and at 21 days of life [52]. PGC1α is a transcriptional coactivator of nuclear receptors that control expression of gluconeogenic enzymes including glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 2 (PEPCK) [53].…”

Section: Iugr Liver Growth and Metabolic Developmentmentioning

confidence: 99%

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Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity

et al. 2009

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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.

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Section: Iugr Liver Growth and Metabolic Developmentmentioning

confidence: 99%

Section: Iugr Liver Growth and Metabolic Developmentmentioning

confidence: 99%

Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity

et al. 2009

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“…These changes affect lipid and glucose metabolism, leading the organism to the preferential use of fatty acids as energy source in order to adapt the organism to a reduced nutrient supply. energy production (Lane et al, 1996), decreasing hepatic oxidative phosphorylation (Ogata et al, 1990) and affecting liver glucose transport (Lane et al, 1999).…”

Section: Animal Evidencementioning

confidence: 99%

Epigenetics and In Utero Acquired Predisposition to Metabolic Disease

2020

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Epidemiological evidence has shown an association between prenatal malnutrition and a higher risk of developing metabolic disease in adult life. An inadequate intrauterine milieu affects both growth and development, leading to a permanent programming of endocrine and metabolic functions. Programming may be due to the epigenetic modification of genes implicated in the regulation of key metabolic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs). The expression of miRNAs in organs that play a key role in metabolism is influenced by in utero programming, as demonstrated by both experimental and human studies. miRNAs modulate multiple pathways such as insulin signaling, immune responses, adipokine function, lipid metabolism, and food intake. Liver is one of the main target organs of programming, undergoing structural, functional, and epigenetic changes following the exposure to a suboptimal intrauterine environment. The focus of this review is to provide an overview of the effects of exposure to an adverse in utero milieu on epigenome with a focus on the molecular mechanisms involved in liver programming.

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“…Beyond global epigenetic effects of IUGR in liver, site-specific increased histone H3 acetylation and reduced nuclear protein levels of HDAC1 and HDAC activity have been identified in promoter sequences of peroxisome proliferator-activated receptor-␥ (PPAR␥) coactivator (Pgc1) and carnitine palmitoyltransferase I (Cpt1) at day 0 of life (19). These changes persisted in IUGR male rats at day 21 of life (19) and correlated with postnatal gene expression levels and subsequent development of insulin resistance in juvenile IUGR rats (37).…”

Section: E21mentioning

confidence: 99%

Epigenetics and developmental origins of diabetes: correlation or causation?

Bansal

Simmons

2018

American Journal of Physiology-Endocrinology and Metabolism

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The incidence of metabolic disorders like type 2 diabetes (T2D) and obesity continue to increase. Although it is evident that the increasing incidence of diabetes confers a global societal and economic burden, the mechanisms responsible for the increased incidence of T2D are not well understood. Extensive efforts to understand the association of early-life perturbations with later onset of metabolic diseases, the founding principle of developmental origins of health and disease, have been crucial in determining the mechanisms that may be driving the pathogenesis of T2D. As the programming of the epigenome occurs during critical periods of development, it has emerged as a potential molecular mechanism that could occur early in life and impact metabolic health decades later. In this review, we critically evaluate human and animal studies that illustrated an association of epigenetic processes with development of T2D as well as intervention strategies that have been employed to reverse the perturbed epigenetic modification or reprogram the naturally occurring epigenetic marks to favor improved metabolic outcome. We highlight that although our understanding of epigenetics and its contribution toward developmental origins of T2D continues to grow, whether epigenetics is a cause, consequence, or merely a correlation remains debatable due to the many limitations/challenges of the existing epigenetic studies. Finally, we discuss the potential of establishing collaborative research efforts between different disciplines, including physiology, epigenetics, and bioinformatics, to help advance the developmental origins field with great potential for understanding the pathogenesis of T2D and developing preventive strategies for T2D.

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Increased Hepatic Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Rat Model of Intrauterine Growth Retardation and Subsequent Insulin Resistance

Cited by 66 publications

References 27 publications

Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity

Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity

Epigenetics and In Utero Acquired Predisposition to Metabolic Disease

Epigenetics and developmental origins of diabetes: correlation or causation?

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