A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice

Epigenetic changes can be induced by adverse environmental exposures, such as nutritional imbalance, but little is known about the nature or extent of these changes. Here we have explored the epigenomic effects of a sustained nutritional change, excess dietary methyl donors, by assessing genomic CpG methylation patterns in isogenic mice exposed for one or six generations. We find stochastic variation in methylation levels at many loci; exposure to methyl donors increases the magnitude of this variation and the number of variable loci. Several gene ontology categories are significantly overrepresented in genes proximal to these methylation-variable loci, suggesting that certain pathways are susceptible to environmental influence on their epigenetic states. Long-term exposure to the diet (six generations) results in a larger number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable. This finding presents the possibility that epigenetic variation within populations can be induced by environmental change, providing a vehicle for disease predisposition and possibly a substrate for natural selection

Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

BACKGROUND: Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice. METHODOLOGY/PRINCIPAL FINDINGS: An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity. CONCLUSIONS/SIGNIFICANCE: Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity

Sex- and Diet-Specific Changes of Imprinted Gene Expression and DNA Methylation in Mouse Placenta under a High-Fat Diet

Changes in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable

Épigénomique nutritionnelle du syndrome métabolique

The importance of epigenetic alterations has been acknowledged in cancer for about two decades by an increasing number of molecular oncologists who contributed to deciphering the epigenetic codes and machinery and opened the road for a new generation of drugs now in clinical trials. However, the relevance of epigenetics to common diseases such as metabolic syndrome and cardiovascular disease was less conspicuous. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with metabolic syndrome (MetS)--combining disturbances in glucose and insulin metabolism, excess of predominantly abdominally distributed weight, mild dyslipidemia and hypertension, with the subsequent development of obesity, type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD)--have suffered improper "epigenetic programing" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their life-time. Moreover, as seen for obesity and T2D, MetS tends to appear earlier in childhood, to be more severe from generation to generation and to affect more pregnant women. Thus, in addition to maternal effects, MetS patients may display "transgenerational effects" via the incomplete erasure of epigenetic marks endured by their parents and grandparents. We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development throughout life. Increasing our understanding on epigenetic patterns significance and small molecules (nutrients, drugs) that reverse epigenetic (in) activation should provide us with the means to he obsolete human thrifty genotype into a "squandering" phenotype

Aqua Walking as an Appropriate and Healthy Winter and Summer Physical Practice? An Exploratory Study

International audience(1) Background: Aqua-walking in a natural environment is a health promoting physical activity that is gaining popularity and appropriate for a variety of populations, however, to date, there is little scientific evidence supporting the efficacy and safety of this activity for older adults. The objective was to propose a preliminary exploration of psychometric and metabolic responses to an acute Aqua walking session either during winter or summer in older adults Aqua walking exercisers. (2) Methods: Heart rate, body temperature, glycemia, and blood pressure were monitored in 37 (30 women, 7 men) participants aged 52 to 83 years old in two Aqua walking sessions (water at 13 °C and 18.5 °C, respectively). Anthropometry (body weight, waist, and hip circumferences), body composition, physical activity level, sedentary time, sleep quality, quality of life, physical self-perception, and perceived health and feelings on various parameters were also assessed. (3) Results: Present results revealed a greater quality of life, physical self-perception, and perceived health in aging Aqua walking exercisers compared to those found in the literature in younger populations. None of the metabolic or psychometric measurements were found to be different between classically calibrated Aqua walking sessions performed in winter compared to summer. By contrast, there was a time effect during the sessions for body temperature (p < 0.001), SBP (p = 0.17), perceived mental and physical well-being (p = 0.006 and p < 0.001, respectively), and anxiety (p < 0.001). Leg discomfort also showed a time effect (p = 0.0009) and interaction effect (p = 0.025). (4) Conclusion: Aqua walking appears here to be an accessible practice that can be performed all year long with a range of physical and mental benefits for older adults. Future studies should investigate the metabolic responses of Aqua walking in different populations

Sex-specific changes in placental gene expression and epigenetic pattern induced by maternal high fat diet

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Dietary alleviation of maternal obesity and diabetes: increased resistance to diet-induced obesity transcriptional and epigenetic signatures.

According to the developmental origins of health and diseases (DOHaD), and in line with the findings of many studies, obesity during pregnancy is clearly a threat to the health and well-being of the offspring, later in adulthood. We previously showed that 20% of male and female inbred mice can cope with the obesogenic effects of a high-fat diet (HFD) for 20 weeks after weaning, remaining lean. However the feeding of a control diet (CD) to DIO mice during the periconceptional/gestation/lactation period led to a pronounced sex-specific shift (17% to 43%) from susceptibility to resistance to HFD, in the female offspring only. Our aim in this study was to determine how, in the context of maternal obesity and T2D, a CD could increase resistance on female fetuses. Transcriptional analyses were carried out with a custom-built mouse liver microarray and by quantitative RT-PCR for muscle and adipose tissue. Both global DNA methylation and levels of pertinent histone marks were assessed by LUMA and western blotting, and the expression of 15 relevant genes encoding chromatin-modifying enzymes was analyzed in tissues presenting global epigenetic changes. Resistance was associated with an enhancement of hepatic pathways protecting against steatosis, the unexpected upregulation of neurotransmission-related genes and the modulation of a vast imprinted gene network. Adipose tissue displayed a pronounced dysregulation of gene expression, with an upregulation of genes involved in lipid storage and adipocyte hypertrophy or hyperplasia in obese mice born to lean and obese mothers, respectively. Global DNA methylation, several histone marks and key epigenetic regulators were also altered. Whether they were themselves lean (resistant) or obese (sensitive), the offspring of lean and obese mice clearly differed in terms of several metabolic features and epigenetic marks suggesting that the effects of a HFD depend on the leanness or obesity of the mother