Fat tissue plays a vital role in the human body, serving functions like energy storage and hormone production. However, the prevalence of obesity worldwide has led to an increase in related health issues, such as type 2 diabetes and cardiovascular disease. University of Michigan researchers are now delving into the fundamental structures of fat tissue, particularly the inflammation linked to obesity, to understand the relationship between fat accumulation and health problems.
Studying fat tissue poses unique challenges because it lacks well-defined layers, making it difficult to categorize cell types and gene expression patterns. In obesity, adipocytes expand and can reach a limit that leads to cell death and inflammation.
To gain a deeper understanding of the immune cell types within adipose tissue during obesity, the researchers fed mice a high-fat diet for 14 weeks. They collected fat tissue samples and used single-cell and spatial analyses to map the mRNA present in the samples.
Through a computational clustering process in the single-cell data, the team identified five types of macrophages. as detailed in the paper published in JCI Insights. These subtypes, named Mac1 to Mac5, exhibited different gene expression patterns and dominated at different stages of obesity. Notably, Mac4 and Mac5, with low pro-inflammatory gene expression, prevailed after 14 weeks of the high-fat diet, while pro-inflammatory Mac2 and Mac3 cells decreased.
This discovery challenges the conventional view that obesity-associated macrophages promote inflammation. The hypothesis is that Mac4 and Mac5 are lipid-associated macrophages (LAMs) aiming to mitigate excessive inflammation and the effects of pro-inflammatory macrophages and dying adipocytes.
The researchers also used spatial transcriptomics to analyze fat tissue structure, identifying structures called crown-like structures that are linked to insulin resistance. They associated the presence of these structures with Mac4 and Mac5 LAMs.
With a better understanding of the cellular composition and spatial organization of fat tissue in obesity, the next phase is to investigate the signaling processes and proteins related to the development of LAMs and metabolic disorders. This research sheds light on the intricate relationship between fat tissue, inflammation, and obesity, offering potential insights for future treatments and interventions.