You are what your mother ate: how food affects gene function

More and more evidence is indicating that diet can affect gene function and that maternal diet can directly affect an offspring’s susceptibility to obesity, diabetes and other metabolic disorders.

In a recent study, a high-fat diet during pregnancy and lactation was found to lead to epigenetic changes in the offspring whereby the adult offspring were more susceptible to obesity and insulin resistance (the precursor to type 2 diabetes). The metabolic pathways affected are regulated by the gut hormone gastric inhibitory polypeptide (GIP).

While this study was on mice, the study leader Andreas Pfeiffer of the German Institute of Human Nutrition (DIfE) asserts that similar mechanisms cannot be ruled out in humans as the maternal diet is not changing the basic DNA structure but rather chemically altering the methylation of the DNA nucleotides (DNA methylations occur when methyl groups bind to the DNA and either activate or inactivate genes).

As scientists throughout the world observe, children of obese mothers have a higher risk of obesity and metabolic disorders. Recent findings suggest that diet-related epigenetic effects may also play a causal role in this. Since humans and mice are genetically very similar, many scientists use mouse models to study such relationships under controlled conditions. Such studies on humans are not possible.

This study focused on the epigenetic effects on the GIP-regulated metabolic pathways that are triggered by the maternal diet during pregnancy and lactation. GIP is a hormone that the gut releases after food intake and which stimulates the secretion of insulin from the pancreas. It influences the metabolism of fat cells and fat oxidation in skeletal muscles and as anabolic hormone promotes the build-up of body mass. These effects are mediated by the GIP via the GIP receptor. If this receptor is lacking as in the Gipr-/- mouse, the hormone can no longer exert its natural effect, and the animals are normally protected from obesity and insulin resistance. Since the Gipr-/- mouse model is well suited for the study of GIP-regulated metabolic pathways, the researchers used this mouse strain for their study. The wild-type strain of the mouse model served as the control.

First, the researchers divided the mouse mothers into three groups, who were fed different chow during pregnancy and lactation:

• Group 1: Gipr-/- mice who received a high-fat diet.
• Group 2: Gipr-/- mice who received regular chow.
• Group 3: Wild-type mice with intact GIP receptor who received regular chow.

After weaning, all offspring of the three groups were fed normal chow for 22 weeks followed by a high-fat diet for an additional 20 weeks.

As the scientists observed, the adult offspring of groups 1 and 3 gained a significant amount of fat mass during the 20-week high-fat diet although they ate less than the offspring of group 2. They also had heightened levels of cholesterol, glucose and insulin in the blood. In addition, they exhibited increased adipose tissue inflammation and enlarged fat cells and oxidised less fat in their muscles. Furthermore, the researchers found that the activity of different genes was altered in group 1 and 3 in comparison to group 2. These genes play a role in fat oxidation in muscles and in inflammatory processes in adipose tissue or are involved in the regulation of energy consumption by the brain.

“The altered gene activity could partially be traced back to DNA methylation, that is, epigenetic changes,” said Pfeiffer. “Our results indicate that the GIP also plays a role in energy consumption, which is controlled by the brain, probably indirectly by reducing the insulin sensitivity of the hypothalamus,” the endocrinologist added. This is an entirely new finding. It remains to be seen to what extent these results can be applied to humans. More research on this topic is needed. However, it is clear that diet not only has a direct influence on the individual, but also may affect the offspring.

Fundamental epigenetic mechanism schematic. Image credit: ©DIfE

DNA methylations (DNA-Methylierungen) occur when methyl groups bind to the DNA. These can either activate or inactivate genes. Nucleosome (Nukleosom): Eight histone proteins form the core of a nucleosome, around which 147 base pairs of a DNA strand are wound. Histone tail (Histon-Ende): The tails of the histone protrude from the nucleosome and can be modified by epigenetic factors. Thus, the binding of the DNA to the corresponding nucleosome is changed, so that the DNA, for example, is accessible to transcription enzymes and a specific gene is activated. Epigenetic factors (Epigenetische Faktoren) alter histone tails eg, by transferring methyl or acetyl groups to lysine side chains. This can hinder or facilitate the activation of a gene. The direct methylation of the DNA permanently changes gene expression when it occurs in the control regions of genes (so-called CpG islets), which are made accessible through the modification of the histones.

Michael Kruse and Farnaz Keyhani-Nejad were the lead authors when this study was reported in the journal Diabetes. The study involved scientists from the German Center for Diabetes Research (DZD) in collaboration with researchers from Helmholtz Zentrum München.

 Top image credit: ©Monika Olszewska/Dollar Photo Club

Originally published here.