High Fat Diet Induces Epigenetic Changes in Offspring

Home » Female » High Fat Diet Induces Epigenetic Changes in Offspring

High fat diet induces epigenetic changes in offspring

Maternal high-fat-diet exposure is associated with elevated blood pressure and sustained increased leptin levels through epigenetic memory in offspring

Using a high fat diet rat model, a study was carried out to investigate the effect of maternal hyperlipidemia in ones offspring, specifically blood pressure and leptin levels, which are indicators of vascular health. Initial findings were then analysed in actual children born to mothers with altered triglyceride levels during pregnancy to confirm or contradict the findings.

For this study forty, 8 week old, Sprague-Dawley were randomly separated into 2 groups: normal control diet or high fat diet. All virgin female rats then mated with normal male rats and continued their allocated diet till delivery. Following delivery the high fat diet offspring were given the same diet as control offspring with various measurements taken, at different time intervals (3 weeks, 8 weeks, 6 months, 1 year), to track development.

Initial serum analysis of female rats confirmed that maternal lipid levels, including triglycerides, total cholesterol and LDL was significantly higher, in the high fat diet rats with no effect on glucose or insulin levels.

As predicted the high fat diet exposed pups weighed significantly more at birth and 3 weeks of age but surprisingly not at 8 weeks of age or later up to 1 years of age. MRI imaging also confirmed no difference in the subcutaneous or visceral adipose tissues of 8 week old pups from both groups. However systolic blood pressure measurements in both male and female pups, exposed to the high fat diet, showed a significant upward trend as they developed, with 1 year old pups displaying significantly enhanced contraction, and significantly reduced relaxation, in response to to vascular tests.

Consequently leptin levels in both serum and adipose tissue was significantly higher in the male and female pups, from the high fat diet group, at all ages (3 weeks, 8 weeks, 6 months, 1 year). DNA methylation analysis of the leptin gene, confirmed that methylation levels (of the leptin gene) in the adipose tissue was significantly altered among the high fat diet exposed offspring. Lastly isolated mesenchymal stem cells, treated with palmitic acid, showed that elevated levels of free fatty acids during adipogenesis contribute to the reprogramming of leptin levels in rat mesenchymal stem cells.

Next 121 preschool age children were recruited to test the association between hyperlipidemia and elevated blood pressure in humans. Corresponding mothers were classified as low maternal Triglyceride (≤ 3.28 mM) or high maternal Triglyceride (> 3.28 mM).

Retrospective analysis confirmed that children born to mothers, with high maternal Triglyceride, were also significantly heavier at birth. Interestingly systolic and pulse pressures was only significantly higher in the male children of affected mothers and not in the female children. Similarly leptin levels was also elevated in the same male children, even though BMI scores did not actually differ between the males in either group. Further analysis confirmed a positive association between maternal Triglyceride levels and leptin levels, in the male children.

To test this association further, 1824 children and 3079 adults were recruited. Comprehensive analysis of this new cohort found;

  • Higher maternal Triglyceride levels in the macrosomia group (birth weight ≥ 4000g)
  • Higher mean systolic and diastolic pressures in adults classified macrosomia at birth
  • Higher prevalence of hypertension (32.46% vs 14.98%) in adults classified macrosomia at birth
  • Higher levels of leptin at all ages, accounting for BMI, in the macrosomia group

Finally leptin gene methylation was then analysed in both newborn and preschool age children. As predicted earlier, DNA methylation of the leptin promoter in lymphocytes was significantly reduced in both groups of children born to mothers with high maternal Triglyceride levels.


According to this study, eating fatty foods when pregnant alters lipid levels (triglycerides, total cholesterol, LDL) resulting in children with higher birth weights and levels of leptin, along with higher mean systolic and diastolic pressures, ultimately increasing the risk of hypertension.


  1. Testing of lymphocytes instead of adipose tissue for leptin methylation

Similar studies

Graf A E, et al. (2016). Maternal high fat diet exposure is associated with increased hepcidin levels, decreased myelination, and neurobehavioral changes in male offspring. https://doi.org/10.1016/j.bbi.2016.08.005

Simonds S E, et al. (2014). Leptin mediates the increase in blood pressure associated with obesity. https://doi.org/10.1016/j.cell.2014.10.058

Turdi S, et al. (2013). Interaction between maternal and postnatal high fat diet leads to a greater risk of myocardial dysfunction in offspring via enhanced lipotoxicity, IRS-1 serine phosphorylation and mitochondrial defects. https://doi.org/10.1016/j.yjmcc.2012.12.007

Marcovecchio M L, et al. (2012). An independent effect of parental lipids on the offspring lipid levels in a cohort of adolescents with type 1 diabetes. https://doi.org/10.1111/j.1399-5448.2012.00860.x


Low Sperm Count Overview

Low sperm count, also known as oligospermia or oligozoospermia, happens when a man has 15 million or less sperm per millilitre (mL) of…. Read more

Causes of Low Sperm Count

The causes of low sperm count fall into 3 main categories: medical, environmental and lifestyle. Medical causes of low sperm count include…. Read more

Questions or comments?