Findings in mice could provide insights into health conditions associated with obesity
Credit: Tushar P. Patel, Ph.D., Jack Yanovski, M.D, Ph.D., Section on Growth and Obesity, NICHD/NIH
A receptor found on liver cells plays an important role in how the body processes and stores fats, suggests a mouse study by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The melanocortin 3 receptor (MC3R) sets off a cascade of actions in liver cells, among them chemical processes that affect whether lipids (fats) inside liver cells are stored or shuttled in the bloodstream to fuel various metabolic reactions.
Researchers found that genetic differences in MC3R in mice may result in a buildup of fats in the liver. The findings could one day lead to advances in treating childhood obesity, fatty liver disease, and cardiovascular disease.
The study was led by Tushar P. Patel, Ph.D., Joo Yun Jun, Ph.D., Jack Yanovski, M.D., Ph.D., and colleagues in the NICHD Section on Growth and Obesity. It appears in Nature Communications.
Background
In the central nervous system, MC3R is involved with energy metabolism and the onset of puberty. Genetic differences in MC3R in people have also been linked to obesity, childhood growth, appetite, and other factors that suggest a role in regulating body weight and body fat, or adiposity.
Results
For the current study, researchers investigated whether MC3R plays a direct role in fat metabolism in the liver. They studied mice with inactivated MC3R and mice with a human version of MC3R that is linked to obesity. They found that these animals had malfunctioning autophagosomes—cellular structures that play a role in recycling damaged proteins, lipid droplets, and other components of cells.
Autophagosomes from mice with altered MC3R had difficulty breaking down lipid droplets—structures that store lipids and other molecules involved in energy metabolism. Restoring MC3R in the liver cells of these mice restored the function of their autophagosomes, reduced the accumulation of lipids in their tissues, and reduced their body weight.
Significance
“By understanding how the body processes and stores fat in the liver, we hope to find ways to reduce harmful fat buildup and circulation linked to obesity,” said Dr. Patel. “This research could lead to treatments that improve fat balance and overall health, especially in children with obesity.”
Reference
Patel TP, et al. Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity. Nature Communications DOI: 10.1038/s41467-025-56936-1 (2025)
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