The Role of Epigenetic Mechanisms in the Development of Obesity

2020 ◽  
Vol 62 (2) ◽  
pp. 103-108
Author(s):  
Marta Pacholczyk ◽  
Ewelina Dzwonkowska ◽  
Tomasz Ferenc
Keyword(s):  
Metabolic Disease ◽  
Body Weight ◽  
Later Life ◽  
Methylation Pattern ◽  
Targeted Prevention ◽  
Obese People ◽  
Early Postnatal Development ◽  
Exercise Interventions ◽  
Increased Risk

Obesity is an important medical and civilization problem due to health consequences and increasing incidence. The development of obesity is influenced by genetic and environmental factors. Despite intensive research the results of which allowed to identify genetic variants predisposing to the development of obesity, the knowledge about the genetic basis of this metabolic disease still remains incomplete. Furthermore, the contribution of single polymorphic gene variants to shaping the obesity phenotype is minimal and accounts for a small part of body weight variability. The need for further research in the field of obesity etiology has increased the interest in the role of epigenetics as a mediator of gene-environment interactions, underlying the development of obesity and related comorbidities. Epigenetics deals with changes in gene expression that are not related to changes of the nucleotide sequence in DNA. Epigenetic modifications include DNA methylation, post-translational modifications of histone proteins and synthesis of non-coding microRNA (miRNA). There is growing evidence indicating that environmental exposures (among others the influence of nutrients) in prenatal and early postnatal development may induce permanent changes in the epigenome, predisposing to an increased risk of obesity in later life. Epigenome-Wide Association Study (EWAS) allowed to indicate differences in the methylation pattern of genes in obese people compared to healthy subjects with normal body weight as well as to identify the first epigenetic markers of obesity in humans. EWAS also allowed to recognize epigenetic changes under the influence of nutrients, during weight loss and occurring during exercise interventions. Significant progress in epigenetic studies on the causes of obesity will allow to predict the risk for this metabolic disease already at a young age and it gives the possibility of introducing targeted prevention strategies.

scholarly journals Maternal antioxidant treatment prevents behavioural and neural changes in offspring exposed to prenatal social stress

2019 ◽  
Author(s):  
H Scott ◽  
TJ Phillips ◽  
Y Sze ◽  
A Alfieri ◽  
MF Rogers ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Prenatal Stress ◽  
Social Stress ◽  
Maternal Stress ◽  
Later Life ◽  
Neuronal Cultures ◽  
Antioxidant Treatment ◽  
Foetal Brain ◽  
Increased Risk

AbstractMaternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. However, the mechanism through which the effects of maternal stress are transmitted to the foetus is unclear. Using a rat model, we explored the mechanisms by which maternal social stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress increased circulating corticosterone in the mother, but not the foetuses. Maternal stress also induced oxidative stress in the placenta, but not in the foetal brain, and this was prevented by administration of a nanoparticle-bound antioxidant. Moreover, antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in the adult male offspring, along with several stress-induced neuroanatomical, neurochemical and gene expression changes in the offspring brain. Importantly, many of these neural effects were mimicked in neuronal cultures by application of placental-conditioned medium or foetal plasma from stressed pregnancies. Both placental-conditioned medium and foetal plasma contained differentially abundant extracellular microRNAs following prenatal stress. The present study highlights the crucial role of the placenta, and the molecules it secretes, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.

scholarly journals A Review of the Potential for Cardiometabolic Dysfunction in Youth with Spina Bifida and the Role for Physical Activity and Structured Exercise

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kevin R. Short ◽  
Dominic Frimberger
Keyword(s):  
Physical Activity ◽  
Spina Bifida ◽  
Cardiometabolic Risk ◽  
Metabolic Risk ◽  
Metabolic Dysfunction ◽  
Exercise Interventions ◽  
Adult Disease ◽  
Increased Risk

Children and adolescents who have decreased mobility due to spina bifida may be at increased risk for the components of metabolic syndrome, including abdominal obesity, insulin resistance, and dyslipidemia due to low physical activity. Like their nondisabled peers, adolescents with spina bifida that develop metabolic risk factors early in life have set the stage for adult disease. Exercise interventions can improve metabolic dysfunction in nondisabled youth, but the types of exercise programs that are most effective and the mechanisms involved are not known. This is especially true in adolescents with spina bifida, who have impaired mobility and physical function and with whom there have been few well-controlled studies. This paper highlights the current lack of knowledge about the role of physical activity and the need to develop exercise strategies targeting the reduction of cardiometabolic risk and improving quality of life in youth with spina bifida.

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 Subjective mental health, incidence of depressive symptoms in later life, and the role of epigenetics: results from two longitudinal cohort studies

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Perna ◽  
Yan Zhang ◽  
Pamela R. Matias-Garcia ◽  
Karl-Heinz Ladwig ◽  
Tobias Wiechmann ◽  
...  
Keyword(s):  
Mental Health ◽  
Depressive Symptoms ◽  
Older People ◽  
Predictive Value ◽  
Meta Analysis ◽  
Later Life ◽  
Increased Risk ◽  
Mental Hrqol ◽  
Subjective Mental Health

Abstract The role of self-perceived general health in predicting morbidity and mortality among older people is established. The predictive value of self-perceived mental health and of its possible biological underpinnings for future depressive symptoms is unexplored. This study aimed to assess the role of mental health-related quality of life (HRQOL) and of its epigenetic markers in predicting depressive symptoms among older people without lifetime history of depression. Data were based on a subgroup (n = 1 492) of participants of the longitudinal ESTHER study. An epigenome-wide association study (EWAS) of mental HRQOL was conducted using DNA from baseline whole blood samples and logistic regression analyses were performed to assess the predictive value of methylation beta values of EWAS identified CpGs for incidence of depressive symptoms in later life. The methylation analyses were replicated in the independent KORA cohort (n = 890) and a meta-analysis of the two studies was conducted. Results of the meta-analysis showed that participants with beta values of cg27115863 within quartile 1 (Q1) had nearly a two-fold increased risk of developing depressive symptoms compared to participants with beta values within Q4 (ORQ1vsQ4 = 1.80; CI 1.25–2.61). In the ESTHER study the predictive value of subjective mental health for future depressive symptoms was also assessed and for 10-unit increase in mental HRQOL scores the odds for incident depressive symptoms were reduced by 54% (OR 0.46; CI 0.40–0.54). These findings suggest that subjective mental health and hypomethylation at cg27115863 are predictive of depressive symptoms, possibly through the activation of inflammatory signaling pathway.

Pre-Eclamptic Pregnancies: An Opportunity to Identify Women at Risk for Future Cardiovascular Disease

2008 ◽  
Vol 4 (2) ◽  
pp. 133-135 ◽  
Author(s):  
Iasmina M Craici ◽  
Steven J Wagner ◽  
Suzanne R Hayman ◽  
Vesna D Garovic
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Meta Analysis ◽  
Later Life ◽  
Future Studies ◽  
Increased Risk ◽  
All Cause Mortality ◽  
History Of

Evaluation of: Bellamy L, Casas JP, Hingorani AD, Williams DJ: Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Br. Med. J. 335(7627), 974 (2007). Evidence has emerged over the years suggesting that women who develop hypertensive pregnancy disorders, most notably pre-eclampsia, are at an increased risk for cardiovascular disease later in life. In this study, a systematic review and meta-analysis were performed, assessing the future risks of cardiovascular disease, cancer and all-cause mortality in women with a history of pre-eclampsia and eclampsia. Women with a history of pre-eclampsia or eclampsia, compared with women without such a history, had an increased risk for cardiovascular disease, including a fourfold increased risk for hypertension, a twofold increased risk for ischemic heart disease, stroke and deep venous thrombosis, and a 1.5-times higher all-cause mortality. The study suggests that affected women may be eligible for preventive therapies at an earlier age, especially if future studies establish the role of pre-eclampsia as an independent cardiovascular risk factor.

scholarly journals Effect of maternal diet on the epigenome: implications for human metabolic disease

2011 ◽  
Vol 70 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Karen A. Lillycrop
Keyword(s):  
Metabolic Disease ◽  
Epigenetic Regulation ◽  
Disease Risk ◽  
Maternal Diet ◽  
Later Life ◽  
Communicable Diseases ◽  
Non Communicable Diseases ◽  
Increased Risk ◽  
Postnatal Environment ◽  
Nutritional Environment

The rapid increase in the incidence of chronic non-communicable diseases over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now considerable evidence that the fetal and early postnatal environment also strongly influences the risk of developing such diseases in later life. Human studies have shown that low birth weight is associated with an increased risk of CVD, type II diabetes, obesity and hypertension, although recent studies have shown that over-nutrition in early life can also increase susceptibility to future metabolic disease. These findings have been replicated in a variety of animal models, which have shown that both maternal under- and over-nutrition can induce persistent changes in gene expression and metabolism within the offspring. The mechanism by which the maternal nutritional environment induces such changes is beginning to be understood and involves the altered epigenetic regulation of specific genes. The demonstration of a role for altered epigenetic regulation of genes in the developmental induction of chronic diseases raises the possibility that nutritional or pharmaceutical interventions may be used to modify long-term cardio-metabolic disease risk and combat this rapid rise in chronic non-communicable diseases.

scholarly journals Pemanfaatan sekolah sebagai sarana pencegahan obesitas sejak dini pada remaja

2019 ◽  
Vol 1 (2) ◽  
pp. 107
Author(s):  
Harry Freitag Luglio Muhammad
Keyword(s):  
Obesity Prevention ◽  
Prevention Program ◽  
Health Workers ◽  
Later Life ◽  
Prevention Programs ◽  
School Based ◽  
Increased Risk ◽  
Obesity Prevention Programs ◽  
Obesity Prevention Program

Obesity among adolescents is a new nutritional problem in Indonesia. This is not only associated with increased risk for obesity in later life but also increased the risk for cardiovascular diseases, type 2 diabetes mellitus, hypertension, and other non-communicable diseases. Therefore an effective and integrated obesity prevention program is highly warranted. There are several community-based programs for obesity prevention that have been developed in the past few decades and school-based activity is one of the potential programs that could be implemented in the Indonesian setting. School is a strategic location for obesity prevention programs in the adolescents because school is the place where most of the adolescents spending their time outside their home. In addition, a school also a centralized community where health and nutrition promotion programs can be done at the same time. In 2012, the Indonesian Ministry of Health published a guidebook on the prevention and treatment of adolescents with obesity at school. However, this guideline only focusing on the role of health workers at puskesmas level and not detailing the role of the school in managing obesity prevention program. Thus, this review was made to provide an alternative solution for obesity prevention in adolescent via programs that can be done at school. Author aimed this review for school managers, puskesmas health workers, the local department of health, researcher and non-government organization that has the concern regarding adolescents health especially in relation to nutrition. This review can be a foundation for the development and implementation of school-based obesity prevention programs as well as a reference for the development of school policy.

scholarly journals Target groups for the prevention of late-life anxiety

2007 ◽  
Vol 190 (5) ◽  
pp. 428-434 ◽  
Author(s):  
Filip Smit ◽  
Hannie Comijs ◽  
Robert Schoevers ◽  
Pim Cuijpers ◽  
Dorly Deeg ◽  
...  
Keyword(s):  
Risk Factors ◽  
Later Life ◽  
Risk Groups ◽  
Chronic Illnesses ◽  
Anxiety And Depression ◽  
Targeted Prevention ◽  
Target Groups ◽  
Health Gains ◽  
Increased Risk ◽  
Anxiety Depression

BackgroundAnxiety disorders in older people are highly prevalent, yet there is little evidence to guide targeted prevention strategies.AimsTo identify subgroups at increased risk of developing anxiety in later life.MethodAnxiety was measured with the Hospital Anxiety and Depression anxiety sub-scale in 1931 people aged 55–85 years followed over 3 years. Risk factors were identified that had a high combined attributable fraction, indicative of substantial health gains when the adverse effect of the risk factors can be contained.ResultsFactors significantly associated with increased risk of developing anxiety included sub-threshold anxiety depression, two or more chronic illnesses, poor sense of mastery, poor self-rated health and low educational level.ConclusionsThe identified risk groups are small, thus providing prevention with a narrow focus, and health gains are likely to be more substantial than in groups not exposed to these risk factors. Nevertheless, more research is needed to produce evidence on target groups where prevention has optimal impacts.

scholarly journals Role of the kidney in the prenatal and early postnatal programming of hypertension

2010 ◽  
Vol 298 (2) ◽  
pp. F235-F247 ◽  
Author(s):  
Michel Baum
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Animal Models ◽  
Adverse Events ◽  
Renin Angiotensin System ◽  
Later Life ◽  
Low Birth Weight Infants ◽  
Increased Risk

Epidemiologic studies from several different populations have demonstrated that prenatal insults, which adversely affect fetal growth, result in an increased incidence of hypertension when the offspring reaches adulthood. It is now becoming evident that low-birth-weight infants are also at increased risk for chronic kidney disease. To determine how prenatal insults result in hypertension and chronic kidney disease, investigators have used animal models that mimic the adverse events that occur in pregnant women, such as dietary protein or total caloric deprivation, uteroplacental insufficiency, and prenatal administration of glucocorticoids. This review examines the role of the kidney in generating and maintaining an increase in blood pressure in these animal models. This review also discusses how early postnatal adverse events may have repercussions in later life. Causes for the increase in blood pressure by perinatal insults are likely multifactorial and involve a reduction in nephron number, dysregulation of the systemic and intrarenal renin-angiotensin system, increased renal sympathetic nerve activity, and increased tubular sodium transport. Understanding the mechanism for the increase in blood pressure and renal injury resulting from prenatal insults may lead to therapies that prevent hypertension and the development of chronic kidney and cardiovascular disease.

scholarly journals Adipocyte-Specific Ablation Of PU.1 Promotes Energy Expenditure and Ameliorates Metabolic Syndrome In Aging Mice

2021 ◽  
Author(s):  
Keyun Chen ◽  
Alejandra De Angulo ◽  
Xin Guo ◽  
Aditya More ◽  
Scott A. Ochsner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Composition ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Later Life ◽  
And Function

ABSTRACTObjectiveAlthough PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of age-associated metabolic syndrome.MethodsWe generated mice with adipocyte specific PU.1 knockout, assessed metabolic changes in young and aged PU.1fl/fl (control) and AdipoqCre PU.1fl/fl(aPU.1KO) mice, including body weight, body composition, energy expenditure and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.ResultsaPU.1KO mice have elevated energy expenditure at a young age and decreased adiposity and increased insulin sensitivity in later life. Corroborating these observations, transcriptional network analysis indicated the existence of validated, aPU.1-modulated regulatory hubs that direct inflammatory and thermogenic gene expression programs.ConclusionsOur data provide evidence for a previously uncharacterized role of PU.1 in the development of age-associated obesity and insulin resistance.

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