Abstract: The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be transmitted across generations is essential for the implementation of initiatives aimed at curbing the current obesity and diabetes crisis.
Alex’s Notes: The beginning of this review is so good I have to quote it,
Obesity and its metabolic sequelae may prove to be the greatest threat to human lifestyle and health in the developed world this century. The obesity epidemic has seen the incidence of being overweight almost double in Western societies in the past two decades and… The rates at which these metabolic disorders have increased over recent time suggests that environmental (e.g., epigenetic) and behavioural effects, rather than genetic causes, are underpinning the present epidemic.
Forget everything and think for a moment – critical thinking. We were never meant to become obese. If we became even slightly overweight in ancestral times, our chance of survival and reproduction would be significantly reduced. It is not our genetics that are creating the health problems; it is the environmental influences that are manipulating gene expression towards more unfavorable outcomes. Yes, we do have the genes to be fat and unhealthy, but evolution would never purposely express such detrimental traits. However, in today’s vastly different world we are programming our genes with permanent adjustments to our homeostatic systems to ensure our immediate survival in this adverse environment.
Two such adaptive responses are DNA methylation and histone methylation, both of which are essential for proper gene expression, and both of which require methyl donors from dietary folate, methionine, and choline, as well as the presence of vitamins B6 and B12. It has been shown that maternal intake of folate or choline influences DNA methylation and gene expression of the offspring and it appears that the period of genetic plasticity extends into early infancy. A potential outcome is an increased risk for a range of metabolic and health disorders, most of which may not manifest until adulthood.
An excellent example of environmental influence comes from genetically identical twins that show dramatically different health states depending on life history differences. Furthermore, individuals who were exposed to famine prenatally showed less gene expression for insulin-like growth factor 2 (IGF-2) than their unexposed siblings, and these changes were specific for periconceptional exposure, reinforcing the importance of early development in establishing and maintaining epigenetic changes. On the other hand, paternal obesity has also been associated with hypomethylation of IGF-2, and newborns of obese parents have altered DNA methylation patterns in general. IGF-2 is critical for growth and development of the fetus. To make matters worse, these changes are compounded over time as those with these disadvantageous traits continue to reproduce, which is counter to evolutions survival of the fittest mantra.
What the above should make perfectly clear is that you are not responsible for only your health, but also the potential health status of your children and grandchildren and so on. Both parents not only pass their genetics and expressed traits onto future generations, but the environment that the children is exposed both while in the womb and during early infancy will continue to manipulate which genes are turned on and off, for better or worse. A low-protein maternal diet during pregnancy may lead to insulin resistance of the offspring later in life, and maternal deficiencies in folate, choline, and other methyl donors hinder fetal development. After birth, overnutrition during the suckling period can lead to skeletal muscle insulin resistance and reduction in GLUT-4 levels, which are important for the uptake of glucose into the muscle. Work in primates has also shown that maternal obesity during pregnancy can alter the structure of the DNA.
So what is the solution? Exercise is a promoter of gene expression that favors mitochondrial health, and high dietary intake of methyl donors both during pregnancy and while breastfeeding is protective. In fact, methyl donor supplementation could even prevent transgenerational amplification of obesity, so if you have a fat history it is possible to break the chain. Overall, it is prudent we acknowledge that evolution is still occurring. Our health and habits can and do influence our offspring’s genetic code and its expression. Exercise and an ancestral diet are paramount to help get the human species back on track.