Epigenetic Insights on Nutrition, Hormones and Eating Behavior

Family Eating Two Parents One Child One Baby Epigenetics

It is widely acknowledged that alterations of the intrauterine and early postnatal nutritional and hormonal environment can make individuals more susceptible to the development of diseases in later life, a phenomenon clearly explained by epigenetics.

We know that what the mother eats during pregnancy can increase the risk of the baby becoming obese as an adult, among other several health disorders. However, the link between these two is much more complex than we thought, as epidemiological and animal studies have revealed a strong relationship between early life nutrition, hormonal environment and the consequent ‘malprogramming’ of the neuroendocrine system which regulate body weight, food intake, and metabolism. 1  2

Regulation of food intake

In humans, eating behavior and control of food intake are regulated by a multitude of neural and hormonal signals, which interact with the central nervous system and more specifically with the hypothalamus, the part of the brain that regulates appetite, satiety, and energy expenditure. 3

This region of the brain is made up of several groups of neurons interconnected with each other. Some of these neurons are located in the arcuate nucleus (ARC) and the paraventricular nucleus (PVN), 3  the first one being the main appetite-regulatory site. At the same time, the ARC contains two subpopulations of neurons that have opposite actions on food intake: the agouti-related protein (AgRP) and neuropeptide Y (NPY) which promote feeding; along with the proopiomelanocortin or POMC  which promotes weight loss and is stimulated by anorexigenic factors. The expression and release of these neurons respond directly to a variety of hormonal and nutrient signals, including leptin, insulin, and glucose.2 3 4

Eating behavior programming

Research suggests that a series of epigenetic mechanisms might regulate the appetite and reward signals to guarantee an adequate and continuous calorie intake during early postnatal life. 5

In an extensive review published in the journal Diseases last year, the authors explored the epigenetic role of milk, including human breast milk, and its influence on health and disease. They reviewed studies on mice where milk intake was associated with the overexpression of FTO, a gene related to increased body weight and adiposity. FTO overexpression triggers ghrelin signaling,  an orexigenic neuropeptide, thus enhancing appetite and suckling in the newborn to secure food intake in the postnatal period, a requirement for proper growth and development. 5

Experimental studies lead by Desai at the Michael Ross’s laboratory have found that food restriction and a high-fat diet during pregnancy might not only increase a baby’s risk for obesity later in life, but they can also induce dysfunction of the hypothalamic appetite/satiety pathway. In both scenarios, appetite regulation is inclined toward orexigenic neurons and away from anorexigenic neurons. This is evidently translated into hyperphagia and increased adiposity which are contributory factors to the development of programmed obesity. 6

On the same line, Chang and colleagues demonstrated a profound effect on the expression of orexigenic peptides like galanin and melanin-concentrating hormone due to a maternal fat-rich diet during gestation and overeating in early life.  The authors concluded that prenatal exposure to a high-fat diet, even for a short period, was enough to produce long-term effects and program the PVN neuropeptides to an enhanced preference for dietary fats and consequently increased weight gain. 7

Other studies in rats suggest that overfeeding during those critical periods can induce a malprogramming of the hypothalamic NPY system. The rats that exhibited hyperphagia and obesity were also less responsiveness to leptin, meaning that at the same time, there’s a resistance to the circulating satiety hormones.6 8

Interestingly, these prenatal acquired long-term alterations might be attributable to an increase in CpG content in the promoter regions of the neuropeptides and receptors involved in these neuroendrocrine functions. Thus, they are potential candidates for methylation-dependent alterations of the expressivity. 9

Insulin matters too

Hormones like insulin, leptin, and cortisol are of crucial importance too. When hormones circulate in our bodies at abnormal levels during critical periods of development, they can induce a permanent malprogramming of the neuroendocrine system leading to a wide range of metabolic disorders and diseases throughout life.9

For example, when insulin circulates in non-physiological concentrations during perinatal life, it may program the development of obesity and diabetes. Hyperinsulinism at this stage occurs as a result of maternal obesity and high blood glucose or early postnatal overnutrition. Besides hyperinsulinism, babies might also exhibit hyperleptinemia and leptin resistance. The consequence is a disposition to develop obesity and associated metabolic disorders such as type 2 diabetes and metabolic syndrome. Similar malprogramming may occur due to perinatal hypercortisolism. 4 9

Results from other research suggest that hyperinsulinemia seems to be associated with a persistently increased number of neurons expressing NPY in the ARC, with a positive association between the number of NPY neurons and daily mean food intake and relative body weight. 2 8

However, maternal underfeeding doesn’t seem to be a better scenario, as scientists have concluded that a poor diet during pregnancy will lead to reduced leptin levels during postnatal life and a reduced anorectic effect of leptin. 10

Final thoughts

Taken together, these data suggest that eating behavior can be the result of an adverse early life environment and can have a life-long influence on neuroendocrine mechanisms. Maternal obesity and diabetes, and overnutrition in early life will end up in a perinatally acquired malprogramming of appetite and satiety pathways and might contribute to the occurrence of hyperphagia, obesity, and hyperinsulinemia throughout later life.

There’s always a chance for primary prevention. Most importantly, we need to favor pregnant women and guarantee a safe environment, offer adequate treatment for gestational diabetes and overweight individuals, and avoid early postnatal overfeeding.




  1. McInerny TK. (2014) Breastfeeding, early brain development, and epigenetics–getting children off to their best start. Breastfeed Med. 9(7):333-4.
  2. Plagemann A. (2006) Perinatal nutrition and hormone-dependent programming of food intake. Horm Res. 65 Suppl 3:83-9.
  3. Jauch-Chara K, Oltmanns KM (2014). Obesity–a neuropsychological disease? Systematic review and neuropsychological model. Prog Neurobiol.114:84-101
  4. Bouret, S. G. (2012). Nutritional programming of hypothalamic development: critical periods and windows of opportunityInternational Journal of Obesity Supplements, 2(Suppl 2), S19–S24.
  5. Melnik, B. C., & Schmitz, G. (2017). Milk’s Role as an Epigenetic Regulator in Health and DiseaseDiseases, 5(1), 12.
  6. Wahlqvist, M. L. et. al. (2015). Early-life influences on obesity: from preconception to adolescence. Annals of the New York Academy of Sciences, 1347(1), 1–28.
  7. Chang, G.-Q. et al. (2008). Maternal high-fat diet and fetal programming: Increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 28(46), 12107–12119.
  8. Plagemann A (2005). Perinatal programming and functional teratogenesis: impact on body weight regulation and obesity. Physiol Behav. 86(5): 661-8.
  9. Plagemann A (2008). A matter of insulin: developmental programming of body weight J Matern Fetal Neonatal Med. 21(3):143-8. doi: 10.1080/14767050801929869.
  10. Bouret SG (2010). Role of early hormonal and nutritional experiences in shaping feeding behavior and hypothalamic development. J Nutr. 140(3):653-7

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About Janeth Santiago Rios 4 Articles
Janeth Santiago Rios is a dietitian-nutritionist from Colombia with an MSc in Nutrition and Metabolism from Barcelona and Rovira i Virgili University. Janeth is passionate about healthy eating, writing, and helping others improve their quality of life through nutrition.

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