New faculty member to further explore research linking brain receptor to increased height, early puberty

For the past few decades, scientists have observed a trend of increased height and younger age of puberty onset in humans. Now, research outlining a new pathway in humans linking body fat to puberty onset and growth could provide an explanation as to why these changes are occurring. Their findings could have dramatic implications for diseases and conditions that cause loss of lean mass, delayed growth, and delayed puberty.

Professor Patrick Sweeney, who joined the Department of Molecular and Integrative Physiology this fall, was one of the authors who contributed to the study during his time as a postdoctoral fellow at the University of Michigan Life Sciences Institute. The study was recently published in Nature.

Sweeney said his postdoctoral research mentor, Roger Cone from the University of Michigan, first became interested in studying the melanocortin 3 receptor’s (MC3R) role in reproductive function because the receptor is expressed in many of the brain circuits involved in reproduction. That led their team to study mice that lacked the receptor. Researchers found that although the mice reproduced normally, the animals had delayed puberty and were incapable of responding normally to metabolic challenges.

“But what we did discover is that when we fast mice, when we take food away, normal mice will stop cycling, and their reproductive cycle will be temporarily turned off,” Sweeney explained. “However, in the mice that lack this receptor, when we fast them, they keep cycling, so they don’t have a normal recognition of changes in metabolic state. That suggested that the receptor was really important for communicating the metabolic state to the reproductive circuitry.”

Scientists in the U.K. soon reached out to Cone and Sweeney’s team with the news that they had found the first human that lacked a functional MC3R. Just as the mice had experienced delayed puberty, so, too, had this individual.

“It was kind of a serendipitous thing where we were both working on similar studies, unbeknownst to each other,” Sweeney recalled. “You don’t necessarily expect that things you discover in basic research on a mouse are going to actually be relevant to people. So, when that does turn out, that’s definitely a huge surprise, and it’s a really nice thing to find.”

Sweeney, whose lab at the University of Illinois is studying the neural circuitry connecting feeding, motivation, and emotion, hopes the findings will be relevant to people with conditions such as anorexia nervosa.

“I think there’s definitely a lot of really great opportunity for MC3R stimulation as a way to promote lean mass as well as promote appetite,” Sweeney said. Additionally, he said the findings could prove helpful for people suffering from cachexia, a condition that occurs when a person with cancer (or undergoing treatment) suffer a loss of appetite that leads to poor nutrition and significant loss of weight and muscle mass.

“We’re excited about the lean mass observation, because there aren’t very good strategies for promoting lean mass,” Sweeney said. “There are a lot of diseases and conditions where loss of lean mass is a problem. If there’s a way to promote lean mass, that could be a really helpful therapeutic.”

Ongoing collaborative projects in the Sweeney Lab at the University of Illinois Urbana-Champaign will follow up on the findings in the Nature paper, along with another recent paper published about the brain receptor (MC3R) during Sweeney’s postdoctoral work. These studies aim to determine the mechanisms underlying the role of MC3R in hypothalamic circuitry regulating feeding, metabolism, reproduction, and emotional behavior, with a focus on developing novel therapeutics for metabolic and neuropsychiatric disorders, including obesity, anorexia nervosa, and cancer cachexia.

Written by Jennifer Lask

Read the full research paper.

November 11, 2021 All News