Specialized Nervous System Macrophages Help Maintain Fat Health and Reduce Inflammation with Age

Recent research led by Yale School of Medicine has uncovered a vital role for nerve-associated macrophages—special immune cells residing near fat nerves—in preserving healthy adipose tissue throughout the lifespan of mice. As animals age, they typically experience chronic low-grade inflammation that impairs tissue function and elevates disease risk. The study, titled "Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation," employed sophisticated techniques such as intravascular labeling and single-cell RNA sequencing to identify and analyze distinct macrophage populations within visceral and brown fat tissues in both young and aged mice of both sexes.

The researchers distinguished resident macrophages from circulating myeloid cells by tagging blood cells with a specific marker, allowing precise sorting and profiling of tissue-specific macrophage subsets. This approach revealed several groups, including those associated with blood vessels, lipid processing, interferon responses, and nerve contact. Notably, nerve-adjacent macrophages extended pseudopodia along adipose nerves and expressed features consistent with myelin and nerve interaction.

Age-related changes observed included a decline in vascular-associated macrophages in males and an increase in lipid-associated macrophages in both sexes, alongside the emergence of CD38+ inflammatory macrophages. Importantly, the nerve-adjacent macrophages, marked by CD169 expression, played a crucial role in fat metabolism and inflammation regulation. Removal of these nerve-associated macrophages heightened inflammatory signals and disrupted fat breakdown, leading to decreased activity of key lipases and weight loss in older female mice.

This study highlights the importance of nerve-adjacent macrophages as specialized subsets that support fat health by facilitating lipid metabolism and controlling inflammation, especially during aging. Understanding these cell populations provides valuable insights into the mechanisms driving age-related metabolic decline and opens potential avenues for targeted therapies to combat metabolic and inflammatory diseases.

Source: https://medicalxpress.com/news/2025-09-specialized-macrophages-adipose-nerves-curb.html