scholarly journals Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment

Reproduction ◽  
2014 ◽  
Vol 148 (6) ◽  
pp. R111-R120 ◽  
Author(s):  
Nady El Hajj ◽  
Eberhard Schneider ◽  
Harald Lehnen ◽  
Thomas Haaf
Keyword(s):  
Metabolic Disease ◽  
Gestational Diabetes ◽  
Energy Homeostasis ◽  
Complex Disease ◽  
Maternal Obesity ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Time Windows ◽  
Intrauterine Environment ◽  
Fetal Overnutrition

The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as ‘developmental origins of health and disease (DOHAD)’ or ‘Barker’ hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene–environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10–20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

scholarly journals Update on FXR Biology: Promising Therapeutic Target?

2018 ◽  
Vol 19 (7) ◽  
pp. 2069 ◽  
Author(s):  
Chang Han
Keyword(s):  
Therapeutic Target ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Metabolic Dysfunction ◽  
Energy Status ◽  
Safety Issues ◽  
Attractive Therapeutic Target

Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut–liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

scholarly journals Impact of Early Nutrition, Physical Activity and Sleep on the Fetal Programming of Disease in the Pregnancy: A Narrative Review

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3900
Author(s):  
Jorge Moreno-Fernandez ◽  
Julio J. Ochoa ◽  
Magdalena Lopez-Frias ◽  
Javier Diaz-Castro
Keyword(s):  
Physical Activity ◽  
Environmental Factors ◽  
Maternal Obesity ◽  
Metabolic Diseases ◽  
Sleep Problems ◽  
Current Knowledge ◽  
Post Partum ◽  
Narrative Review ◽  
Perinatal Complications ◽  
Brain Functions

Early programming is the adaptation process by which nutrition and environmental factors alter development pathways during prenatal growth, inducing changes in postnatal metabolism and diseases. The aim of this narrative review, is evaluating the current knowledge in the scientific literature on the effects of nutrition, environmental factors, physical activity and sleep on development pathways. If in utero adaptations were incorrect, this would cause a mismatch between prenatal programming and adulthood. Adequate caloric intake, protein, mineral, vitamin, and long-chain fatty acids, have been noted for their relevance in the offspring brain functions and behavior. Fetus undernutrition/malnutrition causes a delay in growth and have detrimental effects on the development and subsequent functioning of the organs. Pregnancy is a particularly vulnerable period for the development of food preferences and for modifications in the emotional response. Maternal obesity increases the risk of developing perinatal complications and delivery by cesarean section and has long-term implications in the development of metabolic diseases. Physical exercise during pregnancy contributes to overall improved health post-partum. It is also interesting to highlight the relevance of sleep problems during pregnancy, which influence adequate growth and fetal development. Taking into account these considerations, we conclude that nutrition and metabolic factors during early life play a key role of health promotion and public health nutrition programs worldwide to improve the health of the offspring and the health costs of hospitalization.

Glucocorticoid hormones and energy homeostasis

2014 ◽  
Vol 19 (2) ◽  
Author(s):  
Roldan M. de Guia ◽  
Adam J. Rose ◽  
Stephan Herzig
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Metabolic Dysfunction ◽  
Endocrine Control ◽  
Regulatory Pathways ◽  
Glucose And Lipid Metabolism ◽  
Steroid Binding

AbstractGlucocorticoids (GC) and their cognate intracellular receptor, the glucocorticoid receptor (GR), have been characterised as critical checkpoints in the endocrine control of energy homeostasis in mammals. Indeed, aberrant GC action has been linked to a variety of severe metabolic diseases, including obesity, insulin resistance and type 2 diabetes. As a steroid-binding member of the nuclear receptor superfamily of transcription factors, the GR translocates into the cell nucleus upon GC binding where it serves as a transcriptional regulator of distinct GC-responsive target genes that are – in many cases – associated with glucose and lipid regulatory pathways and thereby intricately control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of GC/GR function in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism.

scholarly journals Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Sarah J. Glastras ◽  
Hui Chen ◽  
Carol A. Pollock ◽  
Sonia Saad
Keyword(s):  
Metabolic Disease ◽  
Kidney Disease ◽  
Maternal Obesity ◽  
Disease Risk ◽  
Reproductive Age ◽  
Intrauterine Environment ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Epigenetic Modulation

Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed.

scholarly journals Mediators of Metabolism: An Unconventional Role for NOD1 and NOD2

2021 ◽  
Vol 22 (3) ◽  
pp. 1156
Author(s):  
Megan T. Zangara ◽  
Isabel Johnston ◽  
Erin E. Johnson ◽  
Christine McDonald
Keyword(s):  
Metabolic Disease ◽  
Intracellular Signaling ◽  
Metabolic Diseases ◽  
Calcium Influx ◽  
Current Knowledge ◽  
Cellular Level ◽  
Alcoholic Fatty Liver ◽  
Intracellular Signaling Pathway ◽  
Oxygen Signaling ◽  
Insulin Responses

In addition to their classical roles as bacterial sensors, NOD1 and NOD2 have been implicated as mediators of metabolic disease. Increased expression of NOD1 and/or NOD2 has been reported in a range of human metabolic diseases, including obesity, diabetes, non-alcoholic fatty liver disease, and metabolic syndrome. Although NOD1 and NOD2 share intracellular signaling pathway components, they are differentially upregulated on a cellular level and have opposing impacts on metabolic disease development in mouse models. These NOD-like receptors may directly mediate signaling downstream of cell stressors, such as endoplasmic reticulum stress and calcium influx, or in response to metabolic signals, such as fatty acids and glucose. Other studies suggest that stimulation of NOD1 or NOD2 by their bacterial ligands can result in inflammation, altered insulin responses, increased reactive oxygen signaling, and mitochondrial dysfunction. The activating stimuli for NOD1 and NOD2 in the context of metabolic disease are controversial and may be a combination of both metabolic and circulating bacterial ligands. In this review, we will summarize the current knowledge of how NOD1 and NOD2 may mediate metabolism in health and disease, as well as highlight areas of future investigation.

Epigenetic Issues. The Link Between Microbiota and Gestational Diabetes.

2022 ◽  
Author(s):  
Olimpia Mora-Janiszewska ◽  
Anna Faryniak-Zuzak ◽  
Dorota Darmochwał-Kolarz
Keyword(s):  
Gestational Diabetes ◽  
Human Population ◽  
Metabolic Diseases ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Intrauterine Environment ◽  
Epigenetic Marks ◽  
Growing Body ◽  
Intergenerational Cycle

Gestational diabetes (GDM) is considered a significant and increasing problem worldwide. The growing body of evidence points out that a hostile intrauterine environment in mothers with GDM via epigenetic mechanisms induces "diabetogenic" and "obesogenic" changes in an offspring's DNA. This sets in motion a vicious intergenerational cycle of metabolic diseases gradually deteriorating the health of the human population. One of the most important players in this process seems to be altered microbiota/microbiome. There is a chance that the identification of specific epigenetic marks may provide a key for future diagnostic, prognostic and therapeutic solutions/measures in the field of person-alized medicine. Given the reversibility of most epigenetic changes, an opportunity arises to improve the long-term health of the human population/race. In this manuscript, we aim to summarize available data on epigenetic changes among women suffering from GDM and their progeny in association with changes in microbiome.

scholarly journals Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota

2020 ◽  
Vol 11 ◽  
Author(s):  
Taylor K. Soderborg ◽  
Charles M. Carpenter ◽  
Rachel C. Janssen ◽  
Tiffany L. Weir ◽  
Charles E. Robertson ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Gut Microbiota ◽  
Maternal Obesity ◽  
Metabolic Diseases ◽  
Cell Function ◽  
Immune Cell ◽  
Public Health Problem ◽  
Microbial Composition ◽  
Predictive Values ◽  
Maternal Overweight

Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alter gut microbial composition, diversity, and short-chain fatty acid (SCFA) levels in neonates. We investigated 46 full-term neonates born to normal-weight or overweight/obese mothers with and without GDM, accounting for confounders including cesarean delivery, lack of breastfeeding, and exposure to antibiotics. Gut microbiota in 2-week-old neonates born to mothers with GDM exhibited differences in abundance of 26 microbial taxa; 14 of which showed persistent differential abundance after adjusting for pre-pregnancy BMI. Key pioneering gut taxa, including potentially important taxa for establishing neonatal immunity, were reduced. Lactobacillus, Flavonifractor, Erysipelotrichaceae, and unspecified families in Gammaproteobacteria were significantly reduced in neonates from mothers with GDM. GDM was associated with an increase in microbes involved in suppressing early immune cell function (Phascolarctobacterium). No differences in infant stool SCFA levels by maternal phenotype were noted; however, significant correlations were found between microbial abundances and SCFA levels in neonates. Our results suggest that GDM alone and together with maternal overweight/obesity uniquely influences seeding of specific infant microbiota in patterns that set the stage for future risk of inflammatory and metabolic disease.

scholarly journals Fetal Programming of the Neuroendocrine-Immune System and Metabolic Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
R. E. Fisher ◽  
M. Steele ◽  
N. A. Karrow
Keyword(s):  
Metabolic Disease ◽  
Immune System ◽  
Metabolic Diseases ◽  
The Body ◽  
Intrauterine Environment ◽  
Maternal Malnutrition ◽  
Thrifty Phenotype ◽  
Thrifty Phenotype Hypothesis ◽  
Increased Risk ◽  
The Individual

Adverse uterine environments experienced during fetal development can alter the projected growth pattern of various organs and systems of the body, leaving the offspring at an increased risk of metabolic disease. The thrifty phenotype hypothesis has been demonstrated as an alteration to the growth trajectory to improve the survival and reproductive fitness of the individual. However, when the intrauterine environment does not match the extrauterine environment problems can arise. With the increase in metabolic diseases in both Westernized and developing countries, it is becoming apparent that there is an environmental disconnect with the extrauterine environment. Therefore, the focus of this paper will be to explore the effects of maternal malnutrition on the offspring’s susceptibility to metabolic disorders such as obesity, cardiovascular disease, and diabetes with emphasis on programming of the neuroendocrine-immune system.

Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal

2019 ◽  
Vol 25 (22) ◽  
pp. 2467-2473 ◽  
Author(s):  
Enrique Reyes-Muñoz ◽  
Federica Di Guardo ◽  
Michal Ciebiera ◽  
Ilker Kahramanoglu ◽  
Thozhukat Sathyapalan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Metabolic Diseases ◽  
Nutritional Intervention ◽  
Attractive Alternative ◽  
Special Role ◽  
Dose Frequency ◽  
Nutritional Interventions

Background: Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). Objective: The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. Methods: We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. Results: Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. Conclusion: More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.

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