Pregnant diet can affect multiple generations

New research suggests that even before becomming pregnant, women who eat high-fat, high-sugar diets can predispose multiple generations to metabolic problems, even though their children consume healthy diets.

"Our findings indicate that a mother's obesity can impair the health of later generations," said Kelle H. Moley, MD, the Washington University School of Medicine's, a James P. Crane Professor of Obstetrics and Gynecology and senior author of the study. "This is particularly important because more than two-thirds of reproductive-age women in the United States are overweight or obese."

While other studies have linked a woman's health in pregnancy to her child's weight later in life, a mouse study at Washington University School of Medicine in St. Louis is the first to indicate that even before becoming pregnant, a woman's obesity can cause genetic abnormalities that subsequently are passed through the female bloodline to at least three generations, increasing the risk of obesity-related conditions such as type 2 diabetes and heart disease.

The study is published online June 16 in the journal Cell Reports.

The research shows that a mother's obesity — and its associated metabolic problems — can be inherited through mitochondrial DNA present in the unfertilized oocyte, or egg. Mitochondria often are referred to as the powerhouses of cells because they supply energy for metabolism and other biochemical processes. These cellular structures have their own sets of genes, inherited only from mothers, not fathers.

"Our data are the first to show that pregnant mouse mothers with metabolic syndrome can transmit dysfunctional mitochondria through the female bloodline to three generations," Moley said. "Importantly, our study indicates oocytes - or mothers' eggs - may carry information that programs mitochondrial dysfunction throughout the entire organism."

From six weeks prior to conception until weaning, researchers fed mice a high-fat, high-sugar diet made up of about 60 percent fat and 20 percent sugar.

"This mimics more of the Western diet. Basically, it's like eating fast food every day."

Kelle H. Moley MD, Department of Obstetrics and Gynecology, Washington University School of Medicine, a James P. Crane Professor of Obstetrics and Gynecology, St. Louis, MO, USA,and senior author of the study.

Offspring then were fed a controlled diet of standard rodent chow, which is high in protein and low in fat and sugar. Despite the healthy diet, the pups, grand pups and great-grand pups developed insulin resistance and other metabolic problems. Researchers found abnormal mitochondria in muscle and skeletal tissue of the mice.

"It's important to note that in humans, in which the diets of children closely mirror those of their parents, the effects of maternal metabolic syndrome may be greater than in our mouse model," Moley said.

More research is needed to determine if a consistent diet low in fat and sugar, as well as regular exercise, may reverse genetic metabolic abnormalities.

"Eating nutritiously is critical. Over the decades, our diets have worsened, in large part due to processed foods and fast foods. We're seeing the effects in the current obesity crisis. Research, including this study, points to poor maternal nutrition and a predisposition to obesity."

Kelle H. Moley MD

Abstract Highlights
•Inbred mice fed a high-fat/high-sucrose (HF/HS) diet develop metabolic syndrome
•F1, F2, and F3 offspring from HF/HS-fed dams develop mitochondrial dysfunction
•Proteins involved in mitochondrial dynamics and ETC are misexpressed in F1–F3 pups
•Mitochondrial changes are seen in F1–F2 oocytes, suggesting germline transmission

Summary
Maternal obesity impairs offspring health, but the responsible mechanisms are not fully established. To address this question, we fed female mice a high-fat/high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a control diet. We observed that female offspring born to obese mothers had impaired peripheral insulin signaling that was associated with mitochondrial dysfunction and altered mitochondrial dynamic and complex proteins in skeletal muscle. This mitochondrial phenotype persisted through the female germline and was passed down to the second and third generations. Our results indicate that maternal programming of metabolic disease can be passed through the female germline and that the transfer of aberrant oocyte mitochondria to subsequent generations may contribute to the increased risk for developing insulin resistance.
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Jun 21, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   

The research shows that a mother's obesity — and its associated metabolic problems — can
be inherited through mitochondrial DNA in the unfertilized oocyte, or egg for 3 generations.
Image Credit: Washington University School of Medicine; Cell Reports