Obesity epigenetics

OBJECTIVE: To discuss the recent literature on paternal obesity, focusing on the possible mechanisms of transmission of the phenotypes from the father to the children. SOURCES: A non-systematic review in the PubMed database found few publications in which paternal obesity was implicated in the adverse transmission of characteristics to offspring. Specific articles on epigenetics were also evaluated. As the subject is recent and still controversial, all articles were considered regardless of year of publication...

Disregarding the rising alarm on the hazardous nature of various phthalates and their metabolites, ruthless usage of phthalates as plasticizer in plastics and as additives in innumerable consumer products continues due low their cost, attractive properties, and lack of suitable alternatives. Globally, in silico computational, in vitro mechanistic, in vivo preclinical and limited clinical or epidemiological human studies showed that over a dozen phthalates and their metabolites ingested passively by man from the general environment, foods, drinks, breathing air, and routine household products cause various dysfunctions...

Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA...

AIMS: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex...

In the last 15 years, it emerged that the practice of regular physical activity reduces the risks of many diseases (cardiovascular diseases, diabetes, etc.) and it is fundamental in weight control and energy consuming to contrast obesity. Different groups proposed many molecular mechanisms as responsible for the positive effects of physical activity in healthy life. However, many points remain to be clarified. In this mini-review we reported the latest observations on the effects of physical exercise on healthy skeletal and cardiac muscle focusing on muscle stem cells...

The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is inversely associated with and sedentary behaviour is positively (and independently) associated with an increased risk of more than ten types of cancer, including colorectal cancer (and advanced adenomas), endometrial cancers, and breast cancer. The most consistent dietary risk factor for premalignant and invasive breast cancer is alcohol, whether consumed during early or late adult life, even at low levels...

OBJECTIVE: According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates predispose offspring to white adipose tissue (WAT) accumulation. In rodents, adipogenesis mainly develops during lactation. The mechanisms underlying the phenomenon known as developmental programming remain elusive. We previously reported that adult rat offspring from high-fat diet-fed dams (called HF) exhibited hypertrophic adipocyte, hyperleptinemia and increased leptin mRNA levels in a depot-specific manner...

Transmission of metabolic diseases from mother to child is multifactorial and includes genetic, epigenetic, and environmental influences. Evidence in rodents, humans and non-human primates support the scientific premise that exposure to maternal obesity or high-fat diet during pregnancy creates a long-lasting metabolic signature on the infant innate immune system and the juvenile microbiota which predisposes the offspring to obesity and metabolic diseases. In neonates, gastrointestinal microbes introduced through the mother are noted for their ability to serve as direct inducers/regulators of the infant immune system...

Obesity, defined as excessive accumulation of fat in adipose tissue, is a metabolic disorder resulting from behavioral, environmental and heritable causes. Such malfunction increases the risk of developing hypertension, diabetes, cardiovascular disease, respiratory problems, osteoarthritis and cancer. Meanwhile, the negative impact of obesity on male reproduction is gradually being recognized. According to clinical investigations and animal experiments, obesity is correlated with reductions in sperm concentration and motility, increases in sperm DNA damage and changes in reproductive hormonal levels...

Intrauterine growth restriction (IUGR) is when fetuses and newborn infants have not reached their true growth potential as genetically defined. Fetuses with IUGR develop in a less than ideal environment that leads to epigenetic changes and marks infants' metabolism for the rest of their lives. Epigenetic changes affect insulin-like growth factor-1 (IGF-1) levels and lead to insulin resistance and ultimately to a metabolic syndrome. The metabolic syndrome is a constellation of illnesses that raise one's risk for type 2 diabetes mellitus, coronary artery disease, and ischemic heart disease, including hypertension, dyslipidemia, central obesity, insulin resistance, and inflammation...

BACKGROUND/OBJECTIVES: Obesity and maternal folate deficiency are associated with increased risk for neural tube defects (NTDs). Limited knowledge exists on the impact of folate status or obesity on DNA methylation of genes related to NTD risk and folate metabolism. SUBJECTS/METHODS: Women (18-35y) with normal weight (NW; BMI 18.5-24.9kg/m(2); n=12) and obesity (OB; BMI >30kg/m(2); n=6) were provided FA (800μg/d) for 8-weeks. Serum folate concentration and changes in DNA methylation across 2098 CpG sites in 91 genes related to NTD risk and folate metabolism were examined...

There is increasing evidence that the predisposition for development of chronic diseases arises at the earliest times of life. In this context, maternal pre-pregnancy weight might modify fetal metabolism and the child's predisposition to develop disease later in life. The aim of this study is to investigate the association between maternal pre-pregnancy body mass index (BMI) and miRNA alterations in placental tissue at birth. In 211 mother-newborn pairs from the ENVIRONAGE birth cohort, we assessed placental expression of seven miRNAs important in crucial cellular processes implicated in adipogenesis and/or obesity...

GNAS exons 1-13 encode the biallelically expressed alpha-subunit of the stimulatory G protein (Gαs). Additional transcripts derived from this locus use alternative first exons that undergo parent-specific methylation, thus allowing transcription only from the non-modified allele. Pseudohypoparathyroidism type Ia (PHP1A) is characterized by Albright's Hereditary Osteodystrophy (AHO) and resistance to multiple hormones; this disorder is caused by maternal inactivating mutations involving Gαs exons. In contrast, pseudohypoparathyroidism type Ib (PHP1B) is characterized mostly by resistance to PTH and often mild TSH resistance, usually without AHO features...

BACKGROUND: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer...

Vertical sleeve gastrectomy (VSG) produces sustainable weight loss, remission of type 2 diabetes (T2D), and improvement of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying the metabolic benefits of VSG have remained elusive. According to our previous results, diet-induced obesity induces epigenetic modifications to chromatin in mouse liver. We demonstrate here that VSG in C57BL/6J wild-type male mice can reverse these chromatin modifications and thereby impact the expression of key metabolic genes...

OBJECTIVE: A significant portion of the heritable risk for complex metabolic disorders cannot be attributed to classic Mendelian genetic factors. At least some of this missing heritability is thought to be due to the epigenetic influence of parental and grandparental metabolic state on offspring health. Previous work suggests that this transgenerational phenomenon is evolutionarily conserved in Drosophila. These studies, however, have all depended on dietary paradigms to alter parental metabolic state, which can have inconsistent heritable effects on the metabolism of offspring...

The "Diabesity" epidemic (obesity and type 2 diabetes) is likely to be the biggest epidemic in human history. Diabetes has been seriously underrated as a global public health issue and the world can no longer ignore "the rise and rise" of type 2 diabetes. Currently, most of the national and global diabetes estimates come from the IDF Atlas. These estimates have significant limitations from a public health perspective. It is apparent that the IDF have consistently underestimated the global burden. More reliable estimates of the future burden of diabetes are urgently needed...

Understanding development and maintenance of beige adipocytes provide exciting insights in establishing novel therapies against obesity and obesity-associated disorders. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser required for differentiation and function of adipocytes. Lsd1 is involved in early commitment of preadipocytes, but dispensable for terminal differentiation of white adipose tissue (WAT). In mature adipocytes, Lsd1 responds to different environmental stimuli to alter metabolic function and enable proper thermogenic and oxidative response...

Chronic diseases, including obesity, are major causes of morbidity and mortality in most countries. The adverse impacts of obesity and associated comorbidities on health remain a major concern due to the lack of effective interventions for prevention and management. Precision nutrition is an emerging therapeutic approach that takes into account an individual's genetic and epigenetic information, as well as age, gender, or particular physiopathological status. Advances in genomic sciences are contributing to a better understanding of the role of genetic variants and epigenetic signatures as well as gene expression patterns in the development of diverse chronic conditions, and how they may modify therapeutic responses...

The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors...