Mother’s Power

By Arman and Anaelle

Today’s topic might make you feel a bit depressed but there is hope in the end: We will see all the different ways you are doomed by your parents but mostly your mother.

The one thing you will never have a say in, is your genes. Your parents give you one copy of each gene and will create your own unique genotype. If we take a closer look, we almost all have the same genome to the exception of some small mutations that makes the whole difference. Let’s take the Ob gene for example. A mutation on this gene can cause an uncontrollable feeling of hunger in these individuals without any control on it, their organism is ‘starving’ because it is never receiving the information that it is getting food, pretty horrible right? That can be explained by the fact that this mutation, Ob/Ob, leads to a dysfunction of leptin production and so your body never naturally produce it. Another way to have this phenotype is with the Db/Db genotype: You have no Leptin receptors in the brain! This is a good reminder that many factors can affect the same pathway, and just the presence or absence of a hormone is not conclusive.

Now we have barely touched on what Leptin is involved in… Leptin could be what we call a super hormone. It is absolutely necessary in the regulation of your appetite, it also plays a major role during your development and is of great importance for reproduction. To be fair, it never works alone but without it, your life wouldn’t be pretty.

Leptin communicates in majority to three nucleus of the Hypothalamus: The Arcuate nuclei (ARC), the Ventromedial Hypothalamic nuclei (VMH) and the ParaVentricular Nuclei (PVN). Just as an overview, our Hypothalamus takes care of our most survival functions: Fighting, Fleeing, Feeding and Sex, but also of our endocrine systems!

Let us explain a bit this whole hypothalamic feeding circuitry. In the ARC, you can find NPY/AgRP neurons, aka orexigenic neurons (“To eat”) and POMC neurons, aka anorexigenic neurons (“Not to eat”), which project mainly to the PVN. We could describe the ARC as the one receiving the message from the hormones and the PVN the one actually doing something with it through behavioral and homeostatic changes.

As we love to play with genes and transcription factors, scientist knockout (“turned off”) some of the known genes/transcription factors involved in the development of these nucleus. The main idea out of these experiments is the notion of “Cell fate” and timepoints. The progenitors, which are stem cells but that have limited replication, of AgRP/NPY and POMC neurons share a common path, and at some point will differentiate either in AgRP/NPY or POMC. This differentiation, that we will call cell fate is still very unclear and many factors interact with it. So most of the knockouts lead to a change in cell fate, leading to a reduced/over expression of POMC or NPY/AgRH neurons but rarely though apoptosis (cell death) or a reduction of the creation of new neurons (neurogenesis).

A very important aspect when we talk about development is the timepoint of these transcription factors/proteins. Prenatally, the moment of the knockouts of the various proteins leads to different consequence on the development of the neurons. For example, a gene involved in transcription factors is the Ngn3 gene. The progenitors of the Ngn3-expressing cells are important in the expression of POMC neurons in the early prenatal period but not in late prenatal period. This shows us the importance of Ngn3 expression in the early development of the POMC.

The knockouts are done experimentally will you say so why is it important? Knowing the interactions that are at stake for the development of the brain, and mainly the hypothalamus in this case, is critical to understand how the metabolism of the mother during pregnancy (and even maybe before pregnancy!) can impair the offspring’s development.

Yes, what your mother eats or does not eat can have neurological impact on you, as well as is she is in obese state or with other metabolic disorders. In these experiments, some mice offsprings showed hyperphagia, which is an excessive drive for food intake since birth. This example is just to demonstrate how your own behavior is biased since birth and this through genetic or metabolic disorders !

One interesting factor that your mother’s diet can have on you is hyperphagia. It can manifest as a result of the amount of food and the types of food she consumes. If your mother consumes a restrictive food diet, hyperphasia can be explained by a decrease in POMC (“Not to eat”) expression and increased NPY (“to eat”) expression.Interestingly, another way that you could become hyperphagic is if your mother is diabetic (Insulin resistant). In a study it was found that mice who were injected with STZ, to induce diabetes, early in pregnancy were more likely to have increased appetite but also have higher chances of obesity and hyperglycemia. This time, there is paradoxically an increase of POMC neurons but attenuated leptin sensitivity (“satiety hormone”).

Potentially the most harmful diet choice your mother could make is low protein diet. If your mother has a diet that is restricted in protein the offspring may have lower volume in certain brain regions and also may have hyperphagia and glucose intolerance. But we don’t know for certain if there are problems within these areas, in this case there may have been reduced volume but there is increased density. It is an area that should be further investigated and could be relevant in ensuring that individuals eating low protein diets are not harming the outcomes of their offspring.

Other studies are starting to show how prenatal diet impacts other brain regions like the hippocampus, possibly causing spatial learning and memory impairments.

After you read all of that, you might want to be tempted to blame all of your problems on your parents, but you still have a say in all of this! Many of those studies showed that if the HFD stopped during childhood and adolescence, the impairments, at least for spatial learning and memory could improve or disappear during adulthood! There is no reason to think that your mother’s diet can doom you to being overweight, or having reduced brain matter. While it certainly plays a role there are protective factors such as exercise and a healthy diet.