The medical school identifies the placental protein as a possible regulator of birth weight

New findings from the University of Minnesota School of Medicine are helping to figure out why some people are likely to be overweight and develop type 2 diabetes, and it starts in the womb.

Previous association studies have shown that low birth weight among infants is a determining factor for eventual obesity and type 2 diabetes. The placenta of low birth weight babies has low levels of mTOR (mechanistic target of rapamycin), and the placenta of older babies has higher levels of mTOR. Based on this research, a study from the U of M Medical School, published in JCI Insight, is the first to directly involve mTOR, a nutrient-sensing protein in the placenta, as a possible regulator of birth weight for a baby.

“It is clear from human and preclinical studies that type 2 diabetes has fetal origins, but we still do not know the mechanisms of how this programming of metabolic dysfunction or type 2 diabetes occurs,” said author Emilyn Alejandro, Ph.D. .D. , associate professor in the Department of Integrative Biology and Physiology. “Our study is the first to show a direct role of a placental protein, such as mTOR.”

They found that in preclinical studies:

• After removing mTOR in the placenta, female offspring had a lower birth weight and had one increased risk for obesity and insulin resistance in adulthood.
• In contrast, after increasing mTOR signaling in the placenta, adult female offspring they protected themselves from obesity induced by a high-fat diet.

“A causal relationship between placental mTOR and the metabolic health of the offspring had not been tested before, and our study suggests that manipulating mTOR in the placenta “It is enough to cause a permanent and lasting impact on the health trajectory of the offspring,” said Brian Akhaphong, first author and post-high school student at Alexander Lab. “Our hope is that we can identify proteins that we can therapeutically target through maternal health to reduce the prevalence of type 2 diabetes.”

The research team will continue their study, investigating which metabolic tissues of the offspring are permanently affected by placental mTOR signaling. Megan Beetch, Ph.D., a postdoctoral fellow, will examine epigenetics, or hereditary changes in gene expression, that do not involve changes in the underlying DNA sequence.