
Li Li
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. 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, which
is 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, about 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 says. “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.

