Obese Mouse Mothers Cause Heart Problems in Offspring

A diet rich in fats and sugars is known for its harmful effects on the heart. Scientists have now discovered that a diet high in fat and sugar in pregnant mothers before and during pregnancy poses problems to the heart of their offspring and that these problems are transmitted at least three generations, even though the younger generations only eat standard diet for mice.

The study, from the Washington University School of Medicine in St. Louis, is published on March 22 in the newspaper AJP-Cardiac and Circulatory Physiology.

The study also suggests that diet-induced cardiac changes in offspring are not only transmitted to offspring by their mothers. The male offspring of obese mothers who mated to healthy women and fed on a normal diet also transmitted the same heart problems. The specific changes in the heart of this offspring were evident in the energy plant modifications of cardiac muscle cells, called mitochondria.

"We know that obesity in pregnant women increases the risk of heart problems for their children," said lead co-author Kelle H. Moley, MD, professor of obstetrics and gynecology. "But we have shown, at least in mice, that these heart problems are not limited to one generation, they are transmitted by the male and female children of obese mothers, even when they have a normal diet. surprise – the problems with cardiac mitochondria seemed to be able to be transmitted only by women, through the mitochondrial DNA present in the egg that we only inherit from our mothers.

"Now that we have shown that mouse fathers also transmit this information, we must begin to study the changes in the nucleus DNA, both in the egg and in the sperm, in order to fully understand all contributing factors, "she said.

In particular, the researchers found multigenerational heart problems, even when the offspring of mice were not obese and had a normal diet throughout their lives. The researchers noted that although they may reveal some effects of a healthy diet, the severity of heart problems has decreased slightly over the generations.

Cardiac abnormalities induced by maternal obesity included cardiac mitochondria that appeared small and fragmented and consumed less oxygen than their normal counterparts. The hearts of most children, although not all, have also shown an increase in the weight of the left ventricle, the main pumping chamber of the heart. In humans, increased left ventricular weight is often a sign of poor quality heart muscle that predisposes to heart failure, a life-threatening condition in which the heart does not pump blood as well as he should.

"Heart abnormalities seem to dissipate a bit across the generations, which is intriguing," said coauthor of the first author, Abhinav Diwan, MD, an badociate professor of medicine. "Echocardiographic problems and increased left ventricular mbad were less evident in the females of the most recent generation we studied, and there were differences in male and female hearts that we did not have. We can not explain for the moment.This study presents questions that it does not answer, and we plan to continue to study these mice to help answer them. "

The researchers also used in vitro fertilization to implant fertilized eggs from obese mice in normal-weight mice to carry out pregnancies. This offspring also showed cardiac malformations, demonstrating that the problems are specific to the egg of the mother's origin fed diet high in fats and sugars, and not the gestational environment during the pregnancy or badfeeding.

Moley and his colleagues suspect that cardiac mitochondria defects are likely caused by so-called epigenetic changes in the DNA of the original obese mother's eggs. The epigenome is an important layer of genetic regulation that governs the reading and execution of DNA instructions. And, in theory, these epigenetic changes in the egg would be present in every cell of the offspring, including in their male or female reproductive systems. Indeed, previous work in this group has confirmed the existence of mitochondrial problems in skeletal muscle, resulting in metabolic abnormalities throughout the body, such as insulin resistance, in the offspring of mouse mothers. obese and over the next two generations.

The researchers plan to study epigenetic changes in the eggs of obese mothers and offspring tissues to understand what is happening in mitochondria, while highlighting the importance of maintaining a healthy weight before and during the pregnancy.

"A big question that people might have is: What can I do if my grandmother or my great-grandmother was obese?" Said the first author, Jeremie LA Ferey , Ph.D., postdoctoral researcher. "We need further studies to find out if it is possible to reverse these mitochondrial defects, but in general, exercise and a healthy diet are still important for heart health."

Provided by
University of Washington School of Medicine