Excess food to the fetus causes diseases in adult life – 07/11/2023 – Equilibrium

Changes in maternal adipose tissue during fetal development, caused both by lack and excess of food intake, can lead to metabolic diseases in adulthood. This is the warning of an article published in the journal Nature Reviews Endocrinology, which describes the numerous mechanisms involved in a concept known as metabolic programming – in which adipose tissue cells (adipocytes) regulate the exposure to nutrients, bringing long-term consequences.

“These are two opposite cases, but which follow identical mechanisms: metabolic reprogramming. Children of women who went hungry during pregnancy tend to be born with low weight and develop hypertension, alterations in the response to stress, heart problems, greater propensity for diabetes and increased insulin resistance. On the other end, children of women with gestational obesity tend to be born with high weight, but also to present metabolic problems in adulthood”, says José Donato Júnior, professor at ICB-USP (Institute of Biomedical Sciences of the University of São Paul).

In the article, based on different studies – some of them conducted by his research group –, the researcher puts the pieces together to clarify the intricate relationship between adipocytes and metabolic reprogramming. The work is supported by FAPESP through a Thematic Project.

Understanding this step by step can help establish future strategies for the prevention and treatment of metabolic diseases, such as diabetes, obesity, hypertension and dyslipidemia (high cholesterol).

“Understanding these mechanisms makes it possible to carry out interventions, as the manipulation of adipose tissue hormones could be the embryo of future therapies. Take the case of gestational diabetes, for example: despite its high prevalence, there is still no therapy. indication is diet control and, if it is not enough, administering insulin, which is extremely adipogenic [favorece a formação de novos adipócitos] for mother and baby. The responsibility is very much on the mothers. It seems that we don’t give the same attention to maternal care that we give to other diseases”, evaluates the researcher.

Two sides of a coin

Donato explains that, for many years, adipose tissue – the famous fatty tissue – was considered a mere deposit of energy, where fat was stored to be used when needed. This view, however, began to change with studies that found that tissue produces important hormones for controlling metabolism, such as leptin and adiponectin. This class of compounds was named adipokines. It is these substances that mediate between the health of the pregnant woman and the development of the children, especially in an area of ​​research called “developmental origins of health and disease” (DOHaD, in its acronym in English).

According to Donato, more recent studies have also shown that maternal obesity, gestational diabetes and excessive weight gain during pregnancy produce an effect similar to that of malnutrition in the fetus by also affecting the sensitivity and levels of leptin and adiponectin. circulating in the mother and fetus.

“Some of the hormones linked to adipose tissue are low or show changes in their action, as is the case of leptin, which promotes the adaptation of energy expenditure related to scarcity or excess”, he comments.

Donato points out in the text that the hormone probably programs the baby’s metabolism at the beginning of life, controlling the development of neurons that regulate energy balance, inducing permanent changes in the preference for hyperpalatable foods and reducing energy expenditure.

The effects of adiponectin occur in the mother and placenta, regulating fetal exposure to nutrients and, consequently, fetal growth and nutrition, with long-term consequences for metabolism and predisposition to diseases.

This is what scientists call epigenetic changes, that is, biochemical changes in cells caused by environmental stimuli that promote the activation or silencing of genes without causing changes in the individual’s genome. In the case of adipokines, they are capable of altering the ability of some genes to be more or less expressed and also transcription factors that, in turn, affect genes related to how proteins interact with DNA.

“Understanding and identifying the specific mechanisms affected by adipokine signaling that lead to metabolic programming are of fundamental interest to guide the development of future strategies to prevent and treat obesity, diabetes and their numerous comorbidities”, says the researcher.