Mum’s high fat diet affects kids’ circadian, metabolic rhythms

Your body marches to a circadian rhythm – a daily cycle of light and dark orchestrated by several genes. In studies in primates, a group of researchers led by those at Baylor College of Medicine found that a high fat diet in mothers can upset this circadian cycle, which may lead to obesity in the offspring. Researchers from the University of Utah and the Oregon National Primate Research Center of the Oregon Health and Science University in Beaverton were also instrumental in this research that appears in the Journal of the Federation of American Societies for Experimental Biology.

High-fat maternal diet affects histone code in offspring

“We have continued to build on our earlier findings exploring the effects of obesity and high fat diets during pregnancy. In this study, we discovered that the genes in the foetal liver responsible for orchestrating circadian (or light and dark cycle) rhythms with appetite and food intake are significantly altered in offspring from moms on a high fat diet,” said Dr Kjersti Aagaard, assistant professor of obstetrics and gynaecology at BCM and the paper’s senior author.

“We have found that one of these genes, called Npas2, appears to be a key organiser of the circadian system with the metabolic circuitry. What is perhaps most intriguing is that the expression of this gene (as well as other genes in the foetal circadian system) is actually regulated by changes in the foetal histone code (the core set of proteins around which DNA wraps itself). The writing of this histone code in the offspring is regulated by the maternal diet, and a notably abnormal code is written when moms eat a high fat diet. In this way, we believe the fundamental steps to ‘reprogramming’ foetal appetite satiety and circadian rhythms with metabolism may be significantly influenced by what a mum eats during pregnancy.”

Improving diet can reduce risks

However, what was especially notable in Aagaard’s study was that improving the mother’s diet – or that of the offspring – can restore, at least in part, the circadian machinery and reduce the threat of obesity in their futures.

In the study, she and her colleagues evaluated the offspring of the pregnant primates in three groups. One received a high fat diet; a second group ate a normal (or control) diet and a third were fed a high fat diet for five years and then switched to a normal diet. The mothers that were or had been on the high fat diet became obese within two to three years.

Aagaard and colleagues have shown in previous published studies that infants of mothers on the high fat diet developed non-alcoholic fatty liver disease, which predisposes them to conditions that lead to obesity and diabetes. They also showed that the mother’s high fat diet, but not her obesity, changed the histone code. In other work, Dr Aagaard and her group had observed that the mum’s high fat diet (and again to a limited extent, obesity) also alters the foetus’s metabolome or metabolic profile.

They found that exposure to the high fat diet in the uterus altered the levels of the gene Npas2 in the liver of the foetus. This effect on the gene is reversible in the foetuses of mothers who had been fed first the high fat diet and then later changed to a normal diet.

Implications

Aagaard said the findings have three implications:

• The machinery to regulate circadian rhythms exists in the foetuses of primates and is regulated by the diet of their mothers.
• A maternal high-fat diet alters the regulation of this system (an epigenetic event) during development, resulting in non-alcoholic fatty liver disease.
• Improving the diet of the mother or the infant after birth can help restore, at least partially, the circadian rhythm.

“Taken together, these findings suggest that in primates the maternal diet is a powerful orchestrator of foetal metabolism with the circadian cycle,” said Aagaard. “When well harmonised, these systems appropriately regulate appetite satiety (satisfaction). When the histone code coordinating these systems is rewritten, such as with a maternal high fat diet, disharmony and lack of synchronisation ensues. By improving the diet, either prenatally or postnatally, there is the potential to reverse these changes, even in the presence of ongoing obesity in the pregnant mum.”

These studies suggest that while a maternal high fat diet leading to obesity may play an important role in regulating whether a child is more prone to obesity and non-alcoholic fatty liver disease, it is not the sole factor, Aagaard said.

“Improving the diet partially reverses some of these changes and may lessen the risk of childhood diseases both including and related to obesity,” she said. “It is one more step in understanding this critical window of time when the foundation for healthy lives is set. We are merely describing the key molecular ingredients for a lifelong recipe of health.”

(Source: Baylor College of Medicine: FASEB Journal)