New research from the University of Wyoming reveals that the brain cells that control hunger may be far more adaptable during prenatal brain development than scientists previously believed. This discovery could reshape how researchers think about preventing obesity.
Li Li, an assistant professor in the UW Department of Zoology and Physiology, is co-first author of a study published in Neuron, one of the world’s leading neuroscience journals. The paper, titled “Developmental reprogramming in melanocortin neurons modulates diet-induced obesity in mice,” was published Feb. 16, 2026. The study’s findings suggest that susceptibility to obesity may partly originate during early brain development, long before dietary habits or lifestyle factors come into play.
Li’s research focuses on specialized neurons that regulate hunger and satiety (feeling satisfied and not wanting to eat more). Two types of neurons work in opposition: proopiomelanocortin (POMC) neurons promote feelings of fullness, while agouti-related peptide (AgRP) neurons stimulate hunger and seeking food. While scientists have long understood how these neurons function in adult animals, less was known about how they form during early brain development.
Li and his colleagues discovered that the precursor cells that give rise to POMC and AgRP neurons are surprisingly flexible. Rather than being permanently programmed from the start, these precursors can adopt different identities depending on the signals they receive during development. In fact, approximately half of AgRP neurons originate from POMC precursor cells.
To better understand this process, Li and his colleagues studied the gene Orthopedia homeobox (Otp). Otp guides POMC precursors to become AgRP during prenatal brain development.
Under normal conditions, Otp helps establish a balance between hunger-promoting and satiety-promoting neurons calibrated for a world where animals do not have access to very much food. However, when food is plentiful, animals often eat too much and develop diet-induced obesity.
When Li and his colleagues experimentally removed Otp in mice’s POMC precursors while the neurons were still developing, it led to a decrease in AgRP neurons and an increase in POMC neurons. As adults, these mice consumed less overall and were very unlikely to become obese because of their diets. These mice ate an amount that allowed them to maintain a healthy weight, even when more food was available.
“Our study shows that the balance between hunger and satiety neurons is not fixed,” Li said. “Instead, it can be developmentally programmed. This opens the possibility that early-life neural development plays a major role in lifelong metabolic health.”
As obesity rates continue to rise worldwide, identifying how hunger-regulating neurons are established could provide new strategies for preventing metabolic disease before it begins.
