The increased prevalence of obesity and related comorbidities is a major public health problem. While genetic factors undoubtedly play a role in determining individual susceptibility to weight gain and obesity, the identified genetic variants only explain part of the variation. This has led to growing interest in understanding the potential role of epigenetics as a mediator of gene-environment interactions underlying the development of obesity and its associated comorbidities. Initial evidence in support of a role of epigenetics in obesity and type 2 diabetes mellitus (T2DM) was mainly provided by animal studies, which reported epigenetic changes in key metabolically important tissues following high-fat feeding and epigenetic differences between lean and obese animals and by human studies which showed epigenetic changes in obesity and T2DM candidate genes in obese/diabetic individuals. More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations. These studies have also reported epigenetic differences between obese/T2DM adults and healthy controls and epigenetic changes in association with nutritional, weight loss, and exercise interventions. There is also increasing evidence from both human and animal studies that the relationship between perinatal nutritional exposures and later risk of obesity and T2DM may be mediated by epigenetic changes in the offspring. The aim of this review is to summarize the most recent developments in this rapidly moving field, with a particular focus on human EWAS and studies investigating the impact of nutritional and lifestyle factors (both pre- and postnatal) on the epigenome and their relationship to metabolic health outcomes. The difficulties in distinguishing consequence from causality in these studies and the critical role of animal models for testing causal relationships and providing insight into underlying mechanisms are also addressed. In summary, the area of epigenetics and metabolic health has seen rapid developments in a short space of time. While the outcomes to date are promising, studies are ongoing, and the next decade promises to be a time of productive research into the complex interactions between the genome, epigenome, and environment as they relate to metabolic disease.

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Recent developments on the role of epigenetics in obesity and metabolic disease

Epigenetic changes are caused by biochemical regulators of gene expression that can be transferred across generations or through cell division. Epigenetic modifications can arise from a variety of environmental exposures including undernutrition, obesity, physical activity, stress and toxins. Transient epigenetic changes across the entire genome can influence metabolic outcomes and might or might not be heritable. These modifications direct and maintain the cell-type specific gene expression state. Transient epigenetic changes can be driven by DNA methylation and histone modification in response to environmental stressors. A detailed understanding of the epigenetic signatures of insulin resistance and the adaptive response to exercise might identify new therapeutic targets that can be further developed to improve insulin sensitivity and prevent obesity. This Review focuses on the current understanding of mechanisms by which lifestyle factors affect the epigenetic landscape in type 2 diabetes mellitus and obesity. Evidence from the past few years about the potential mechanisms by which diet and exercise affect the epigenome over several generations is discussed.

The role of diet and exercise in the transgenerational epigenetic landscape of T2DM

Epigenetic modification refers to heritable changes in gene function that cannot be explained by alterations in the DNA sequence. The current literature clearly demonstrates that the epigenetic response is highly dynamic and influenced by different biological and environmental factors such as aging, nutrient availability and physical exercise. As such, it is well accepted that physical activity and exercise can modulate gene expression through epigenetic alternations although the type and duration of exercise eliciting specific epigenetic effects that can result in health benefits and prevent chronic diseases remains to be determined. This review highlights the most significant findings from epigenetic studies involving physical activity/exercise interventions known to benefit chronic diseases such as metabolic syndrome, diabetes, cancer, cardiovascular and neurodegenerative diseases.

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Physical activity in the prevention of human diseases: role of epigenetic modifications

Aim: DNA methylation programs gene expression and is involved in numerous biological processes. Accumulating evidence supports transgenerational inheritance of DNA methylation changes in mammals via germ cells. Our aim was to determine the effect of exercise on sperm DNA methylation. Materials & methods: Twenty-four men were recruited and assigned to an exercise intervention or control group. Clinical parameters were measured and sperm samples were donated by subjects before and after the 3-month time-period. Mature sperm global and genome-wide DNA methylation was assessed using an ELISA assay and the 450K BeadChip (Illumina). Results: Global and genome-wide sperm DNA methylation was altered after 3 months of exercise training. DNA methylation changes occurred in genes related to numerous diseases such as schizophrenia and Parkinson's disease. Conclusions: Our study provides the first evidence showing exercise training reprograms the sperm methylome. Whether these DNA methylation changes are inherited to ...

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Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans.

Skeletal muscle is a malleable tissue capable of altering the type and amount of protein in response to disruptions to cellular homeostasis. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signalling mechanisms initiating replication of specific DNA genetic sequences, enabling subsequent translation of the genetic message and ultimately generating a series of amino acids that form new proteins. The functional consequences of these adaptations are determined by training volume, intensity and frequency, and the half-life of the protein. Moreover, many features of the training adaptation are specific to the type of stimulus, such as the mode of exercise. Prolonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fibre-type transformation and substrate metabolism. In contrast, heavy resistance exercise stimulates synthesis of contractile proteins responsible for muscle hypertrophy and increases in maximal contractile force output. Concomitant with the vastly different functional outcomes induced by these diverse exercise modes, the genetic and molecular mechanisms of adaptation are distinct. With recent advances in technology, it is now possible to study the effects of various training interventions on a variety of signalling proteins and early-response genes in skeletal muscle. Although it cannot presently be claimed that such scientific endeavours have influenced the training practices of elite athletes, these new and exciting technologies have provided insight into how current training techniques result in specific muscular adaptations, and may ultimately provide clues for future and novel training methodologies. Greater knowledge of the mechanisms and interaction of exercise-induced adaptive pathways in skeletal muscle is important for our understanding of the aetiology of disease, maintenance of metabolic and functional capacity with aging, and training for athletic performance. This article highlights the effects of exercise on molecular and genetic mechanisms of training adaptation in skeletal muscle.

The molecular bases of training adaptation

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m2 ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation.

https://www.physiology.org/doi/pdf/10.1152/physiolgenomics.00024.2014

Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity

Effect of aerobic exercise on leptin and PGC-1a gene expression in a unique cohort of morbidly obese Polynesians with Type 2 diabetes

Objective: The aim of this investigation was to examine the effect of aerobic and resistance training on the skeletal muscle mitochondrial function. Setting: Wellington Hospital New Zealand, Massey University, Wellington Campus New Zealand. Period: Sep 2008- Sep 2011 Results: There was a very large effect (6.7 ± 1.2) in the AER group for BHAD activity whereas in the PRT group a large effect (2.7 ± 1.2) for BHAD activity was observed. There was an increase in CS activity in both groups (PRT; p = 0.007, AER; p=0.03) however, the activity increase was more in the PRT group (effect size = 1.8 ± 1.3). COX activity was raised in both groups as well though the effect size in the PRT group was 2.3 ± 1.2 meaning a very large change with PRT exercise compared to a moderate effect (1.0 ± 1.2) with AER exercise. Conclusion: Overall these findings suggest that both PRT and AER exercise can be effective therapeutic modalities for the induction of changes at the cellular level in muscle of people with T2DM.

Effect of aerobic and resistance training

.. Objectives: The hypertensive disorders of pregnancy (HDP), especially severe preeclampsia are most common cause of neonatal and maternal mortality and morbidity. Alteration in metabolism of calcium and magnesium during pregnancy is considered to be one of etiological factor for pre-elampsia. Study Design: Case-control study. Settings: Departments of Pathology and Gynecology and Obstetrics, Bahawal Victoria Hospital. Period: September 2018 to June 2019. Material & Methods: To compare whether serum levels of calcium or magnesium showed significant change in mild and severe preeclamptic patients as compared to control group. Research population consisted of pregnant females that were divided into three groups. The mild and severe preeclamptic groups comprised of 55 and 26 participants respectively and 45 were included in control group. The serum calcium and magnesium levels were measured in these groups. Results: Maximum numbers of preeclamptic cases were presented at 28-32 week of gestation while severe pre-eclamptic group showed most cases in 33-36 weeks. In both groups, most of cases occurred in multiparous women as compared to nulliparous women. The normotensive group showed serum calcium and magnesium levels of 9.08±0.63 and2.12±0.22mg/dl while mild preeclamptic (mPE) had mean value of 7.91±0.64 and 1.58±0.42mg/dl and measurement were 7.67±0.48 and 1.26±0.44 in cases of severe pre eclampsia (sPE). Serum magnesium levels were significantly lower in sPE as compared to mPE (<0.0001) while difference was not statistically significant for serum calcium level (0.14). Conclusion: Both decrease level of serum calcium and magnesium might be risk factor in development of preeclampsia with more emphasis on role of low magnesium as a prognostic marker in severe preeclamptic cases.

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Comparative analysis of serum calcium and magnesium as a better predictor in cases of mild and severe pre-eclampsia.

ABSTRACT As antibiotic resistance is increasing daily, the desire to treat an infection without causing any harmful effects assumes increasing importance. Ozone gas is a reactive antioxidant. Its role in blood circulation and uplifting immunity is an ideal complement to achieving curative care treatments. Aside from treatments, the therapeutic and biological effects of ozone may have positive results by reducing tooth demineralization, its antimicrobial capabilities rely upon its ability to oxidize, which produces free radicals, and has immediate action on microbes. The usage of ozone in dentistry is recommended for a variety of purposes, which comprises carious lesion treatments, root canal disinfection, post-surgical treatment, tooth bleaching, periodontal problems, prosthodontics, and orthodontics. Ozone has the potential to be a promising alternative therapy in dentistry. However, well-designed research is needed to analyze ozone’s utilization in the field of dentistry to determine its importance from a clinical perspective so that the general public can benefit from it. This systematic review aims to describe the technique in which ozone can be advantageous as well as the many ways of applications of ozone therapy in dentistry.

Irum Hayat

Papers

Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity

Effect of aerobic exercise on leptin and PGC-1a gene expression in a unique cohort of morbidly obese Polynesians with Type 2 diabetes

Effect of aerobic and resistance training

Comparative analysis of serum calcium and magnesium as a better predictor in cases of mild and severe pre-eclampsia.

Therapeutic Effects and Uses of Ozone in Dentistry: A Systematic Review