New understanding of maternal diet, growth/energy homeostasis

Fruit and vegetables

OHSU researchers define molecular basis to explain link between a pregnant mother’s nutrition and infant growth. 

In a study published online in Nature Communications, a research team led by Jae W. Lee, Ph.D., has demonstrated that two neurons key to growth and metabolism — GHRH and AgRP — are developmentally interconnected.

While many factors, such as the age of the mother, overall health and genetics ultimately play a role, the correlation between a mother’s nutrition habits and metabolism has been proved to directly influence the growth of her child. Findings of this research conducted with a mouse model may take scientists one step closer to knowing why.

Read more about the research on OHSU News.

Located in the hypothalamus, within a grouping of neurons known as the arcuate nucleus, GHRH, or growth hormone-release hormone, neurons orchestrate body growth and maturation. Meanwhile, AgRP, or Agouti-related peptide, neurons stimulate feeding and suppress energy usage.

To understand how these neurons are developed, Lee, professor of pediatrics, Papé Family Pediatrics Research Center, and team cataloged various proteins expressed in the arcuate nucleus of mice and analyzed their overall function.

They found one specific protein — DLX1 — is critical for GHRH neuron development. However, it also suppresses the development of the AgRP neuron. When DLX1 was removed, the mouse’s growth was stunted, yet it appeared obese.

Additionally, DLX1 was found to suppress the development of OTP-labeled cells that become AgRP neurons. This would suggest normal growth development, but limited blockage of energy use, resulting in a trim figure.

These findings prove, for the first time, the intimate relationship between GHRH and AgRP neurons in developmental lineage.

In addition to Lee, OHSU coauthors include Jacob Raber, Ph.D., Department of Behavioral Neuroscience and Soo-Kyung Lee, Ph.D., Papé Family Pediatrics Research Center and Vollum Institute.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke (R01 NS054941) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK064678; R01 DK103661), both components of the National Institutes of Health.

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