Researchers from Vanderbilt University School of Medicine Basic Sciences have made a groundbreaking discovery about the role of the hunger hormone, leptin, in brain development. While earlier studies established that leptin interacts with specific receptors on hunger-related neurons to promote brain circuit development, new findings set to be published in PNAS on November 25 suggest some neurons may be receptive to leptin even without these receptors.

Led by Richard Simerly, Louise B. McGavock Professor of Molecular Physiology and Biophysics, the research team found that the influence of leptin extends beyond just maintaining body weight in adults by suppressing hunger. It plays a vital role in the weeks following birth by helping to shape the brain circuits that regulate fundamental bodily functions.

In particular, the team discovered that turning off the activity of hunger neurons (known as “AgRP” neurons) during the crucial early stages of brain development could leave a lasting impact on the structure and functionality of circuits that manage energy balance.

The research findings suggest that hormonal activity, such as that of leptin, could be involved in defining the arrangement of neural circuits that control essential functions related to metabolic health and disease risk. This indicates that factors influencing neuronal activity could impact brain development more widely than previously thought.

Simerly explains, “The idea that neural circuits controlling something as basic as energy balance could be influenced by activity alone during key developmental stages suggests a range of factors could impact brain development via this mechanism.” He adds that exposure to molecules that alter neural activity during brain development could have long-term implications for brain function in health and disease.

These insights could potentially pave the way for leveraging this mechanism to promote normal brain development and improve outcomes for individuals at genetic risk or those exposed to harmful environmental factors.

This significant research work owes its success to the dedication and expertise of staff scientist Jessica Biddinger, the first author, and the valuable contributions of collaborating author Julio Ayala, Director of the Vanderbilt Mouse Metabolic Phenotyping Center.