Scientists find why obesity could cause inflammation

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The Important Role of Fat

Fat is not just an energy storage in our bodies; it plays vital roles in hormone production and other essential functions.

However, the increase in obesity worldwide, spurred by modern lifestyles, has sparked health concerns, as obesity is linked to other severe conditions like type 2 diabetes and heart disease.

So, understanding fat, particularly its structure and role in obesity-related inflammation, has become a vital scientific pursuit.

Investigating the Hidden Complexities

Lindsey Muir and her team dove into a study to explore the inner workings of fat tissue. The investigation was no easy task due to the tissue’s intricate structure.

Unlike the brain or spinal cord, which has neatly organized layers, fat tissue has cells evenly distributed, making analysis more challenging.

The team used advanced techniques, focusing on single cell and spatial analyses, to peek into the gene expression within fat tissue.

Their study utilized mice, which were fed a high-fat diet for 14 weeks, to examine the changes in their fat tissue and observe the variations at a microscopic level.

In the context of obesity, fat cells enlarge until they reach a breaking point, which leads to cell death and subsequent inflammation.

The team focused on understanding immune cells (specifically, macrophages) in the fat tissue and their spatial relationship during obesity. Macrophages are cells that help tidy up our body by clearing out dead cells and debris.

They discovered that macrophages, known to be present in different subtypes, were more diverse than anticipated.

Identified as Mac1 to Mac5, these subtypes behaved distinctly and emerged at various stages during the progression of the diet. Mac1 was found in both lean and obese mice.

Mac2 and Mac3, associated with inflammation, peaked at 8 weeks into the high-fat diet. Surprisingly, as the diet progressed, Mac4 and Mac5, which have low inflammation-inducing gene expression, became more dominant.

This revelation opens up new perspectives on the role of macrophages in obesity-related inflammation.

Unraveling Surprising Findings

The insights from Muir’s team suggest that there’s more to understand about how macrophages behave in obesity.

Originally, the belief was that the macrophages accumulating during obesity promoted inflammation.

However, these findings tell a more nuanced tale, indicating that certain types of macrophages might actually be trying to mitigate inflammation.

Especially significant was the discovery of Mac4 and Mac5 macrophages, which the team suspects are what are known as Lipid Associated Macrophages (LAMs).

These LAMs might be our body’s way of trying to control damaging inflammation levels caused by other macrophages and dying fat cells.

The research utilized spatial transcriptomics, which allowed the team to analyze unique barcodes attached to mRNA in tissue, mapping gene expression to specific tissue locations.

They searched for specific markers, named crown-like structures, which are linked to insulin resistance, a critical factor in type 2 diabetes.

These structures, once developed, indicate tissue dysfunction and are reluctant to disappear. The LAMs, Mac4 and Mac5, were found to be present where these crown-like structures emerged.

Looking Ahead

Building upon the newfound knowledge of fat tissue’s cellular composition and structure during obesity, Muir and her team plan to dig deeper into exploring the signaling processes and proteins related to LAM development and metabolic disorders.

The broader objective is to unlock more answers, providing valuable insights into tackling obesity and its related health issues from a new angle.

This could pave the way to developing innovative therapeutic strategies to manage or even prevent obesity and its damaging health consequences in the future.

If you care about inflammation, please read studies about the big cause of inflammation in common bowel disease, and vitamin B may help fight COVID-19 and reduce inflammation.

For more information about nutrition, please see recent studies about new way to halt excessive inflammation, and results showing foods that could cause inflammation,

The research findings can be found in JCI Inisight.

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