Methyl donor supplementation prevents transgenerational amplification of obesity

Department of Pediatrics, Baylor College of Medicine, USDA Children's Nutrition Research Center, Houston, TX 77030, USA.
International journal of obesity (2005) (Impact Factor: 5.39). 08/2008; 32(9):1373-9. DOI: 10.1038/ijo.2008.100
Source: PubMed

ABSTRACT The obesity epidemic, recognized in developed nations for decades, is now a worldwide phenomenon. All age groups are affected, including women of childbearing age, fueling concern that maternal obesity before and during pregnancy and lactation impairs developmental establishment of body weight regulatory mechanisms in the fetus or infant, causing transgenerational amplification of obesity prevalence and severity. The biological mechanisms underlying such processes remain unknown.
We used agouti viable yellow (A(vy)) mice to test the hypothesis that maternal obesity induces transgenerational amplification of obesity. We passed the A(vy) allele through three generations of A(vy)/a females and assessed cumulative effects on coat color and body weight. By studying two separate but contemporaneous populations of mice, one provided a standard diet and the other a methyl-supplemented diet that induces DNA hypermethylation during development, we tested whether potential transgenerational effects on body weight might be mediated by alterations in epigenetic mechanisms including DNA methylation.
The genetic tendency for obesity in A(vy) mice was progressively exacerbated when the A(vy) allele was passed through successive generations of obese A(vy) females. This transgenerational amplification of body weight was prevented by a promethylation dietary supplement. Importantly, the effect of methyl supplementation on body weight was independent of epigenetic changes at the A(vy) locus, indicating this model may have direct relevance to human transgenerational obesity.
Our results show that in a population with a genetic tendency for obesity, effects of maternal obesity accumulate over successive generations to shift the population distribution toward increased adult body weight, and suggest that epigenetic mechanisms are involved in this process.

Download full-text


Available from: Michael Travisano, Jan 14, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The number of overweight and obese people is increasing at an alarming rate, especially in the developed and developing countries. Obesity is a major risk factor for diabetes, cardiovascular disease, and cancer, and in consequence for premature death. The development of obesity results from the interplay of both genetic and environmental factors, which include sedentary life style and abnormal eating habits. In the past few years a number of events accompanying obesity, affecting expression of genes which are not directly connected with the DNA base sequence (e.g. epigenetic changes), have been described. Epigenetic processes include DNA methylation, histone modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, as well as non-coding micro-RNA (miRNA) synthesis. In this review, the known changes in the profile of DNA methylation as a factor affecting obesity and its complications are described.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 11/2014; 68:1383-1391. · 0.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early exposure to a fat-enriched diet programs the developmental profile, thus is associated with disease susceptibility in subsequent generations. Chronic low-grade inflammation, resulting from maternal high fat diet, is activated in the fetal environment and in many organs of offspring, including placenta, adipose, liver, vascular system and brain. The prevalence of an inflammatory response is highly associated with obesity incidence, cardiovascular diseases, NAFLD and brain damage. Substantial studies using high-fat model have consistently demonstrated the incidence of such inflammatory reactions; however, the potential contribution of active inflammation toward the physiological outcomes and developmental diseases are neither in depth discussed nor systemically integrated. Therefore, we aim to summarize the current findings in regards to how a maternal high fat diet influences the inflammatory status, and probable pathogenic effects on the offspring. More importantly, since limited research has been conducted to reveal the epigenetic regulation of these inflammatory markers by maternal high fat diet, we sincerely hope our review will not only outline the pathophysiological relevance of inflammation, but also identify a future direction for mechanistic investigation and clinical application.
    The Journal of Nutritional Biochemistry 08/2014; DOI:10.1016/j.jnutbio.2014.06.011 · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is a global epidemic, and maternal smoking has been shown to be associated with the development of childhood obesity. Overall, approximately 40% of children worldwide are exposed to tobacco smoke at home. It is well known that environmental changes within a critical window of development, such as gestation or lactation, can initiate permanent alterations in metabolism that lead to diseases in adulthood, a phenomenon called programming. It is known that programming is based on epigenetic alterations (changes in DNA methylation, histone acetylation, or small interfering RNA expression) that change the expression pattern of several genes. However, little is known concerning the mechanisms by which smoke exposure in neonatal life programs the adipose tissue and endocrine function. Here, we review several epidemiological and experimental studies that confirm the association between maternal nicotine or tobacco exposure during gestation or lactation and the development of obesity and endocrine dysfunction. For example, a positive correlation was demonstrated in rodents between increased serum leptin in the neonatal period and exposure of the mothers to nicotine during lactation, and the further development of leptin and insulin resistance, and thyroid and adrenal dysfunction, in adulthood in the same offspring. Thus, a smoke-free environment during the lactation period is essential to improving health outcomes in adulthood and reducing the risk for future diseases. An understanding of the pathophysiological mechanisms underlying the effects of smoking on programming can provide new insights into therapeutic strategies for obesity.
    Frontiers in Physiology 11/2012; 3:437. DOI:10.3389/fphys.2012.00437 · 3.50 Impact Factor