HEALTH NEWS

Study Title:

Lack of Apetite-Control Brain Cells in Premature Delivery

Study Abstract

A low birth-weight (LBW) offspring exhibits reduced hypothalamic neural satiety pathways and dysregulated signaling leading to programmed hyperphagia and adult obesity. Hypothalamic appetite circuits develop during early life, under the influence of neurotrophic hormones (leptin and insulin). Notably, LBW newborns have reduced plasma leptin and insulin levels. As neurons and glia arise from neuronal progenitor cells (NPC), we postulated that a programmed impairment of NPCs may contribute to reduced hypothalamic neural pathway development in a LBW offspring. Control dams received ad libitum food, whereas study dams were 50% food-restricted from pregnancy day 10 to 21 (LBW). At day 1 of age, hypothalamic NPCs were cultured as neurospheres (NS) and treated with leptin/insulin. We analyzed in vitro NPC proliferation and differentiation into neurons/astrocytes, expression of signal molecules promoting proliferation (activated Notch1 and its downstream target, Hes1) and in vivo NPC proliferation and migration. LBW offspring had impaired in vivo evidence of NPC division and migration, and reduced in vitro evidence of proliferation and differentiation to neurons and astrocytes, under basal and stimulated conditions. The reduced Notch1 and Hes1 expression in LBW neurosphere, under both basal and stimulated conditions, suggests a reduced progenitor cell population or reduced cell density within the neurosphere.

From press release:

Providing further understanding of the link between low birth weights and obesity later in life, researchers found nutritionally deprived newborns are "programmed" to eat more because they develop less neurons in the region of the brain that controls food intake, according to an article published in the journal Brain Research.

The study by a team of researchers at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) suggests that overeating is programmed at the level of stem cells before birth when the mother has poor or inadequate nutrition.

Using an animal model, the researchers found less division and differentiation of the neural stem cells of a newborn with low birth weight as compared to normal birth weight. Previous studies have found a small size at birth followed by accelerated "catch-up" growth is associated with an increased risk of adult obesity, cardiovascular disease, type 2 diabetes, hypertension and osteoporosis.

"This study demonstrates the importance of maternal nutrition and health in reducing obesity," said Dr. Mina Desai, an LA BioMed principal investigator and corresponding author of the new study. "Obesity and its related diseases are the leading cause of death in our society, yet we have few effective strategies for prevention or treatment. These studies suggest maternal nutrition could play a critical role in preventing obesity and related disease."

In addition to obesity, the findings of altered brain (neural stem cells) development suggest that fetal growth restriction may be associated with cognitive and/or behavioral alterations. Importantly, the study offers potential opportunities for prevention and treatment for obesity and other related disorders. In addition to Dr. Desai, LA BioMed investigators Tie Li and Michael G. Ross participated in the study.

More than 60% of American adults are overweight and more than 1 in 5 are obese. Obesity is a serious health concern for children and adolescents, as well. About 17 percent of children and adolescents ages 2-19 years are obese.

Study Information

Mina Desai, Tie Li, Michael G. Ross.
Hypothalamic neurosphere progenitor cells in low birth-weight rat newborns: Neurotrophic effects of leptin and insulin.
Brain Research
2011 March
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center