June 28, 2016

Poor maternal diet affects future generations of mice

At a Glance

  • Female mice fed a high fat, high sugar diet produced 3 generations of female offspring with metabolic problems.
  • The abnormalities may have been inherited through mitochondrial DNA in the mother’s eggs.
  • The findings suggest a mechanism for how a mother’s obesity can affect the health of her descendants.
Electron microscope images of mouse muscle. Muscles from female offspring of mice fed a high fat, high sugar diet (top) had large mitochondria and fat droplets (arrows), compared to offspring of mice fed a control diet (bottom). Moley lab, Cell Reports.

More than half of all pregnant women in the United States are overweight or obese. Babies born to obese mothers are at risk for developing obesity, heart disease, and diabetes as adults. There is some evidence that the grandchildren and great-grandchildren of obese women might also inherit a risk of metabolic problems.

A team led by Dr. Kelle H. Moley at Washington University School of Medicine in St. Louis set out to better understand how a mother’s health influences the health of her offspring. The research was supported by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Results were published on June 28, 2016, in Cell Reports.

The researchers fed female mice a high fat, high sugar diet. The diet was 59% fat, 26% carbohydrate (17% sucrose), and 15% protein. The mice ate the diet for 6 weeks—from before conception until weaning. A control group of mice ate a regular diet of 13% fat, 62% carbohydrate, and 25% protein. 

The female mice mated with male mice fed a regular diet. The scientists monitored the next 3 generations of female offspring. These subsequent generations were all fed a regular diet and mated with males fed a regular diet.

The female mice fed the high fat, high sugar diet became obese and developed metabolic syndrome. They had high blood levels of glucose, cholesterol, and triglycerides.

The female offspring (daughters) born to these obese mothers weren’t obese, but had abnormal glucose and insulin levels compared to the female offspring of mice feed a normal diet. They also had metabolic abnormalities in their fat and muscle tissues.

The scientists found that all 3 generations of female offspring from the mothers that ate the poor diet had abnormal mitochondria in their muscles. Mitochondria produce energy and play a key role in metabolism. They contain their own DNA and are passed from a mother to her daughters.

The daughters and granddaughters of the obese mothers were found to have abnormal mitochondria in their eggs. The researchers surmise that the mother’s diet-induced metabolic disorders may have been passed down through her eggs. The transfer of abnormal mitochondria in the eggs might have contributed to the development of metabolic disorders in the offspring.

“Our data are the first to show that pregnant mouse mothers with metabolic syndrome can transmit dysfunctional mitochondria through the female bloodline to 3 generations,” Moley says. “Importantly, our study indicates oocytes—or mothers’ eggs—may carry information that programs mitochondrial dysfunction throughout the entire organism.”

— by Carol Torgan, Ph.D.

Related Links

References: Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations. Saben JL, Boudoures AL, Asghar Z, Thompson A, Drury A, Zhang W, Chi M, Cusumano A, Scheaffer S, Moley KH. Cell Rep. 2016 Jun 16. pii: S2211-1247(16)30663-5. doi: 10.1016/j.celrep.2016.05.065. [Epub ahead of print]. PMID: 27320925.

Funding: NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).