Maternal High-Fat Diet Linked to Liver Disease in Mice

Mice born to mothers who ate a high-fat diet developed liver fibrosis.

It is known that numerous external factors can influence fetal development. Since maternal intake of certain substances, including tobacco and alcohol, can lead to abnormal fetal development, it is recommended that these substances should be avoided. New studies have explored the link between nutritional intake and fetal outcomes.

A study presented at the Experimental Biology 2017 meeting questions how maternal nutrition during pregnancy and immediately after birth may increase the risk of the offspring developing nonalcoholic fatty liver disease (NAFLD) later in life.

NAFLD is characterized by the build-up of fat in the liver and is the most common liver disease in adults and children. While the disease is associated with obesity, investigators have a poor understanding of why some individuals may develop the condition and others do not.

"Complications of obesity are a significant cost burden for the medical system, especially given the prevalence of obesity," said researcher Michael Thompson, MD, PhD. "Understanding how maternal exposures impact obesity-related disease such as nonalcoholic fatty liver disease will allow us to develop lower cost preventative therapies to utilize up front rather than awaiting complications down the road."

In the study, the authors discovered that the offspring of pregnant mice who consumed a high-fat diet were more likely to develop liver fibrosis. Even when offspring were weaned to a low-fat diet after exposure to a high-fat diet, they went on to develop fibrosis in adulthood, according to the study.

The authors indicated that the livers of the offspring also showed signs of fat accumulation and inflammation, which are characteristics of NAFLD.

These findings suggest that fetal exposure to a high-fat diet can elicit changes in the liver that last until adulthood, despite consuming a low-fat diet after birth, according to the study. This may mean that healthy weight individuals born to mothers who consume a high-fat diet could develop NAFLD.

Further analyses indicated that bile acid levels and genes involved in the regulation of the bile acid were altered in offspring exposed to a high-fat diet in utero. This suggests that offspring may have cholestasis, which is when the normal flow of bile is interrupted, the authors reported.

The authors are now working to gain a better understanding of the mechanisms involved with increased risk of disease progression. The authors also plan to use their findings to determine preventive therapies that could be administer during pregnancy or after birth, according to the study.

"If human offspring from obese mothers have a similar risk for developing fibrosis as we see in mice, we may be able to predict who is going to develop more serious disease," Dr Thompson said. "Knowing who is most at risk for more serious disease will guide us on which patients should be treated more aggressively. Furthermore, understanding the biological mechanisms involved in this increased risk could lead to preventative therapies."