Maternal Diet Programs Metabolism in Offspring

Regular readers will recall the many posts on the issue of intra-uterine epigenetic programming, that is now believed by many to be one of the key drivers of the childhood obesity epidemic.

As more and more human and experimental evidence for this hypothesis accumulates, it is becoming increasingly evident that the intra-uterine environment may play a central role in determining the future risk of obesity in offspring (even much later in life).

This notion is further supported by an interesting study by Ricardo Orozco-Solís and colleagues from the Université de Nantes, France, published in the latest issue of PLoS One, showing that in rats, maternal nutrition during pregnancy is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus (the brain centre that regulates eating behaviours).

In this study, the researchers analyzed the profile of the hypothalamus transcriptome (the sum of all genes expressed as RNAs) in 180 days-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet through pregnancy and lactation.

From the almost 30,000 examined genes, around 700 were up-regulated and 300 down-regulated by early protein restriction.

Most interestingly, the researchers found that perinatal protein restriction permanently altered the expression of two gene clusters regulating a large number of common cellular processes.

While the first gene cluster includes several gate keeper genes regulating insulin signaling and nutrient sensing, the second cluster represents a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel. This network also links temporal and nutritional cues to metabolism through their tight interaction with the circadian clock (in this context readers may recall the recent posts on the link between sleep and obesity).

As pointed out by the authors, these findings clearly show that (protein-) malnutrition during pregnancy and lactation may play a key role in epigenetically programming hypothalamic circuits regulating energy homeostasis.

As blogged before, the key to preventing childhood obesity may well lie in ensuring maternal nutrition and healthy body weights – once born, as with the proverbial horses, the kids may be out of the barn!

Hamilton, Ontario

Orozco-Solís R, Matos RJ, Guzmán-Quevedo O, Lopes de Souza S, Bihouée A, Houlgatte R, Manhães de Castro R, & Bolaños-Jiménez F (2010). Nutritional programming in the rat is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus. PloS one, 5 (10) PMID: 20975839