Studies show that the negative impact on the heart of obesity and diabetes may still be present after several generations.

obesity

Our lifestyle (diet, physical activity…) has consequences on our health… and that of our descendants. An American study showed that obesity-induced heart problems in mice were present in the offspring of obese parents for at least three generations, even if the new generations were not themselves overweight.

“We already knew that a diet that is too fat and sweet has a negative impact on the heart, but now we have seen that these consequences are more serious in offspring than in parents who have consumed this diet,” explains researcher Kelle Moley, a reproductive health specialist at Washington University in St. Louis, USA. In this research, published in the American Journal of Physiology in March 2019, mice were made obese on a diet high in fat and sugar. This led to heart defects in their offspring, while the parents did not have these defects. Even more surprisingly, these heart failures were present up to three generations later, even though the new generations ate a normal diet and were not obese.

Energy deficiencies at the root of heart failure

In an earlier study published in the journal Cell in 2016, Moley and her team found that obesity caused defects in mitochondria (the energy plants of our cells) and that these defects were inherited for several generations. The affected mitochondria may not produce enough energy to supply the heart, leading to heart failure.

“We thought that these heart defects were due to changes in mitochondrial DNA,” which is different from so-called “nuclear” DNA, the DNA located at the heart of our cells in the chromosomes. However, this mitochondrial DNA has the particularity of being transmitted only by the mother. “But in this new study we saw that the father can also transmit these metabolic defects,” says Kelle Moley in astonishment. They are, therefore “not only caused by mitochondrial DNA but also by nuclear DNA, which is important for mitochondrial function and can be transmitted by the father”.

Epigenetic transmission?

However, these would not be modifications directly on genes (or genetic mutations), but on elements that regulate their expression. “Obesity and diabetes affect the epigenome, i.e. all the modifications made to the genome to adapt its expression to the environmental context,” explains Valérie Grandjean, a specialist in gene expression at the University of Nice. To express itself, a gene is first transcribed into RNA, a kind of mobile version of itself that will transmit its “orders” to make proteins. The epigenome modifies this mechanism, without the gene itself being altered.

“These epigenetic elements can be found in the germ cells (oocytes and sperm) of parents, and thus move on to the next generation,” says Valérie Grandjean. Thus, the changes in mitochondrial function caused by obesity would pass to subsequent generations.

But the epigenome constantly adapts to our environment, including our diet. So why do these epigenetic changes persist after several generations, despite the return to a normal diet? Researcher Valérie Grandjean and Bernard Portha, pancreas specialist at the University of Paris-Diderot, made an inventory of the scientific data available on this subject in a journal published in January 2019 in the journal Nutrients. “Several studies show this type of transgenerational transmission, but the exact mechanism is not yet known,” says Bernard Portha, “What this research show is that obesity in our ancestors is a risk factor to be taken into account. But it is not irreversible, with a healthy lifestyle we can compensate for this bad legacy,” concludes Valérie Grandjean.

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