Obesity causes an inflammatory response in adipose tissue

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New research published in JCI Insights, revealed a complex inflammatory response that occurs in adipose tissue during the development of obesity.

Whether adults or children, Obesity rates are increasing According to the World Health Organization, in a matter of “proportion of epidemics”. The increase in obesity rates has been linked to a corresponding increase in cases of type 2 diabetes and cardiovascular disease.

In obesity, fat cells (cells that store energy in the form of lipids) increase. Expanding To store excess energy from meals. When fat cells reach their capacity, cell death and inflammation can occur.

To understand the link between fat accumulation and poor health outcomes in obese people, researchers are investigating the structure of adipose tissue and the mechanisms behind inflammatory responses.

Immune cells in adipose tissue

Researchers behind this new study used single-cell and spatial analysis to understand the location of different immune cell types within adipose tissue and their relationship to each other as obesity progresses. Did.

The researchers fed the mice a high-fat diet for 14 weeks, then harvested adipose tissue for analysis. They used clustering computer models to group cells with similar genetic makeup.

From this analysis, they identified five subtypes of macrophages, a type of immune cell responsible for removing dead cells and cell debris. “We knew that there were likely multiple subtypes of macrophages…What surprised us was that the resulting numbers were very different from each other, appearing at different times and growing over time. It was about becoming more dominant.” Dr. Lindsay Muir, is a research assistant and professor of computational medicine and bioinformatics at the University of Michigan School of Medicine and lead author of the study. Said.

Change over time

The five subtypes of macrophages identified in this study were named Mac1, 2, 3, 4, and 5.

Mac1 was detected in adipose tissue of both obese and normal mice, whereas levels of Mac2 and Mac3 cells were – Both expressed pro-inflammatory genes – The highest value was reached after 8 weeks of feeding mice a high-fat diet.

After feeding mice a high-fat diet for 14 weeks, the number of Mac4 and Mac5 cells, which are characterized by reduced pro-inflammatory gene expression, began to increase, while the number of Mac2 and Mac3 cells decreased.

“The field believes that a type of macrophage that accumulates in obesity promotes inflammatory conditions. Based on these data, there is much more to this story,” Muir said. said.

She has Mac4 cells and Mac5 cells. lipid-associated macrophages (LAM) are a subset of macrophages found primarily in adipose tissue of obese individuals. Here they are protective role Combats fat cell growth, inflammation, and metabolic dysfunction.

Spatial analysis brings new insights

The researchers performed spatial transcriptomic analysis to capture gene expression across thin sections of adipose tissue taken from mice, mapped the location of the mRNA, and imaged the tissue immediately before capturing the mRNA. This allowed visualization of a crown-like structure. Macrophages surrounding dying fat cells are present in a crown-like pattern, indicating adipose tissue dysfunction.

The research team identified that the macrophages within the crown-like structure were derived from the Mac4 and Mac5 subtypes.

This study provides new insights into the cellular and spatial organization of adipose tissue in obesity, but also the cellular signaling processes required to trigger the development of LAM and how LAM contributes to metabolic disorders. Further research is needed to understand whether

reference: Stansbury CM, Dotson GA, Pugh H, Rehemtullah A, Rajapakse I, Muir LA. Lipid-associated macrophage lineages rewire the spatial landscape of adipose tissue in early obesity. JCI Insights. 2023;8(19). Doi: 10.1172/jci.insight.171701

This article is a re-edited version of the published press release. University of Michigan. Material has been edited for length and content.