High-fat diets drive production of inflammatory immune cells in the bone marrow of mice

High-fat diets drive production of inflammatory immune cells in the bone marrow of mice

Scientists have shown that high-fat diets can cause rapid changes in the bone marrow of mice, leading to the production of inflammatory immune cells, according to results published today in eLife.

The findings may help explain how high-fat diets cause inflammation, which can contribute to the development of insulin resistance, type 2 diabetes, and other complications in obese individuals.

The invasion of inflammatory immune cells, called monocytes, into adipose tissue is a hallmark of obesity, but what leads to this harmful phenomenon is not clear. Many immune cells, including monocytes, are produced in the bone marrow, which is highly sensitive to environmental changes. Scientists have already shown that fat cells in the bone marrow expand rapidly in response to a high-fat diet.

We wanted to know if bone marrow tissue an early responder to a high-fat diet could serve as a precursor to the inflammation observed in obesity. Do diet-induced changes high in fat in the bone marrow lead to the production of inflammatory monocytes that invade adipose tissue in obese people? “

Amira Kulaib, Senior Author, and Senior Scientist in Cell Biology at SickKids, and Professor in the Departments of Pediatrics, Biochemistry and Physiology at the University of Toronto, Canada

Klip and colleagues found that mice fed a high-fat diet begin to experience metabolic disturbances throughout the body and in the bone marrow within three weeks. The fat cells multiply in the bone marrow and acquire the characteristics of white fat cells. Metabolic changes in monocytes also occur in bone marrow cells – they use less oxygen to break down sugar into energy, and lactic acid accumulates in the surrounding cells and fluid. The team also found that mitochondria, the cellular factories that break down sugar into energy, break down into pieces inside monocytes and become less efficient. This process of mitochondrial fragmentation is associated with insulin resistance.

Over the course of several weeks, the number of monocytes in the bone marrow changes to include a smaller amount of monocytes called Ly6Ca little to more than one subunit called Ly6Chigh, which is the same type of single cell that invades fat tissue in people with obesity. This accumulation of Ly6Chigh Monocytes start in the bone marrow before monocytes accumulate in fat tissue in the rest of the body to become inflammatory macrophages – the mature form of monocytes.

“These results show that high-fat diets can cause bone marrow fat cells to remodel which disrupts the normal balance of monocytes, and can subsequently lead to invasive Ly6C.high Unicorns seep into the body,” Kleip continues.

The team further demonstrated that white adipose tissue can induce these changes in experiments using cell samples taken from mice fed a high-fat diet. They also found that brown adipose tissue, which is more abundant in thin people, can cause a shift toward non-invasive Ly6C.a little unicorns.

“Our study reveals how high-fat diets cause a cascade of inflammation in the body that includes the bone marrow,” Klip concludes. “More research is needed to further understand this process and see if there are ways to prevent or reverse this process. It will also be important to find out if bone marrow is also an early responder to obesity in humans. Learning more may lead to new therapies to treat obesity. Obesity and the prevention of complications such as diabetes.”


Journal reference:

Boromand, b. et al. (2022) Bone marrow adipocytes drive development of invasive tissue Ly6Chigh Monocytes during obesity. eLife. doi.org/10.7554/eLife.65553.

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