Link between low birth weights and obesity later in life: Altering hormone levels changes cellular development in the brain

Their study using fetal neural stem cells from animal models, which was published online by the journal, Endocrinology, found that altered levels of leptin or insulin may have marked effects on their offspring brain development. The researchers said these findings provide further clues to the causes of obesity.

With more than 60% of American adults overweight and more than one in five obese, researchers are closely examining the causes. Obesity is a serious health concern for children and adolescents, as well. About 17% of children and adolescents ages 2-19 years are obese. In the past, Type 2 diabetes occurred mostly in middle-aged people. Today, this type of diabetes is seen in 11% of children and adolescents.

Leptin and insulin play a role in the body's ability to regulate energy balance, with leptin serving as a long-term appetite regulator. In comparison, insulin is released quickly into the blood stream upon eating and serves as a short-term appetite regulator. In addition, insulin is the hormone that transports glucose across the cell wall so the glucose may be converted to energy.

The researchers found altering the levels of leptin caused neural stem cells from animal model to develop more neurons, while changing the levels of insulin promoted the creation of more astrocytes. Each process occurred at the expense of the development of other brain cells. Importantly, levels of leptin and insulin are altered in infants of mothers with gestational diabetes, obesity or inadequate nutrition during pregnancy.

"This study shows these two hormones influence the makeup of brain cells and how many cells we develop," Mina Desai, PhD, a LA BioMed principal researcher and the corresponding author of the study. "Our cellular makeup is akin to the foundation for a house. If the foundation isn't constructed properly, you can try and fix it but you will still have a problem. The same is true for people with fewer cells to regulate appetite and maintain stable and proper function of brain."

The new study builds on LA BioMed research, published in Brain Research in March, which found nutritionally deprived newborns are "programmed" to eat more because they develop fewer neurons in the region of the brain that controls food intake. That study suggested overeating is programmed at the level of stem cells before birth when the mother has poor or inadequate nutrition. The present results suggest that additional infant and child brain functions may be altered or impaired under conditions of suboptimal pregnancy 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.

"By studying the ways in which leptin and insulin communicate with neural stem cells to divide and direct the cell fate, we may one day be able to come up with a new way to combat obesity," Dr Desai said. "We have few effective methods for preventing or treating obesity, even though it is a leading cause of death in our society."

In addition to Dr. Desai, LA BioMed investigators Tie Li, PhD, and Michael G. Ross, MD, MPH, participated in the study. This work was supported by National Institute of Health Grants R01HD054751, R01DK081756 27 and R03HD060241