New study reveals previously unrecognized immune cell types and interactions in adipose tissue

Fat tissue, often criticized, serves as a vital, complex organ essential for energy storage and hormone production. Unfortunately, our modern lifestyles have led to a global obesity epidemic, accompanied by conditions like type 2 diabetes and cardiovascular disease.

Researchers, including Lindsey Muir, Ph.D., and Cooper Stansbury, a Ph.D. candidate from the University of Michigan, are exploring the intricacies of fat tissue structure and the inflammation linked to obesity. Their study, titled “A lipid-associated macrophage lineage rewires the spatial landscape of adipose tissue in early obesity,” published in JCI Insight, employs single cell analysis and spatial transcriptomics to uncover previously unknown immune cell types and their interactions within adipose tissue.

Studying fat tissue poses unique challenges because it lacks defined cell layers found in organs like the brain or spinal cord. In obesity, fat cells (adipocytes) expand and can lead to inflammation and cell death.

To gain insights into immune cell types in adipose tissue, the researchers fed mice a high-fat diet over 14 weeks, collected fat tissue samples, and used single cell and spatial analyses to examine the mRNA present in the samples. Through clustering in the single cell data, they discovered a surprising diversity among macrophages, immune cells responsible for cleaning up debris and dead cells. They identified five macrophage subtypes: Mac1, 2, 3, 4, and 5. These subtypes exhibited different behaviors over time, challenging the prevailing belief that obesity-associated macrophages solely promote inflammation.

It’s hypothesized that Mac4 and Mac5, with low pro-inflammatory gene expression, may represent lipid-associated macrophages (LAMs) and might be involved in mitigating inflammation from pro-inflammatory macrophages and dying adipocytes.

The researchers then conducted meticulous sectioning of fresh frozen fat tissue, utilizing spatial transcriptomics to map gene expression to specific tissue locations. They focused on identifying crown-like structures, associated with insulin resistance, and found these structures to be linked to the presence of Mac4 and Mac5 LAMs.

With a deeper understanding of fat tissue’s cellular composition and spatial organization in obesity, the next phase involves investigating the signaling processes and proteins related to the development of LAMs and metabolic disorders.

Source: University of Michigan

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